ArticleLiterature Review
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

Cannabis is the most popular illicit drug in the Western world. Repeated cannabis use has been associated with short and long‐term side effects including respiratory and cardiovascular disorders, cognitive alterations, psychosis, schizophrenia and mood disorders. However, casual relations between cannabis use and these adverse effects are missing. On the other hand, recent research proposed promising therapeutic potential of cannabinoid‐based drugs for a wide range of medical conditions including neurological and psychiatric disorders. The current article presents a contemporary review on the adverse effects, safety and the therapeutic potential of cannabis and cannabinoid‐based drugs. Given the growing popularity in the use of cannabinoid‐based drugs for both recreational and medical purposes and their potential harmful effects, there is a need for further investigation in this field. This article is protected by copyright. All rights reserved.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... Cannabis, scientifically known as Cannabis sativa L. from the family Cannabaceae, has been cultivated for ages and utilized as a potential source of fiber, oil, protein, and popularly, psychoactive and medicinal purposes [1]. Historically, cannabis products have been illicitly grown for recreational and social activities to appreciate their euphoric effects [2]. Cannabis contains more than 120 active compounds, which are classified to belong in a secondary metabolite group known as phytocannabinoids or cannabinoids [3] of which cannabidiol (CBD), ∆9-tetrahydrocannabinol (THC), cannabigerol (CBG), and cannabinol (CBN) are the most studied [4]. ...
... Trichomes are glandular membranes containing secondary metabolites, phytocannabinoids, and terpenes, and are found to be most abundant on the surface of the cannabis inflorescence. Extracts or products of cannabis have been studied for the treatment of different illnesses including neurological and psychiatric disorders [2], prevention of vomiting and nausea of cancer patients, boosting of hunger in acquired immunodeficiency syndrome (AIDS) patients [7], and the treatment of muscle spasms, spasticity and neuropathic pain, and chronic pain [8]. On the other hand, hemp has been produced for textiles, biocomposites, papermaking, biofuel, functional foods, and cosmetics [6]. ...
... Aside from positive effects, cannabis has been shown to cause detrimental health impacts in humans. Continuous usage of cannabis has been found to cause a variety of immediate and long-term detrimental consequences, including cardiovascular and respiratory problems, behavioral impairment, psychosis, schizophrenia, and mental illnesses [2]. People with cannabis use disorder have problems such as extreme mood shifts and memory-loss-related and concentration issues [11]. ...
Article
Full-text available
In recent years, cannabis (Cannabis sativa L.) has been legalized by many countries for production, processing, and use considering its tremendous medical and industrial applications. Cannabis contains more than a hundred biomolecules (cannabinoids) which have the potentiality to cure different chronic diseases. After harvesting, cannabis undergoes different postharvest operations including drying, curing, storage, etc. Presently, the cannabis industry relies on different traditional postharvest operations, which may result in an inconsistent quality of products. In this review, we aimed to describe the biosynthesis process of major cannabinoids, postharvest operations used by the cannabis industry, and the consequences of postharvest operations on the cannabinoid profile. As drying is the most important post-harvest operation of cannabis, the attributes associated with drying (water activity, equilibrium moisture content, sorption isotherms, etc.) and the significance of novel pre-treatments (microwave heating, cold plasma, ultrasound, pulse electric, irradiation, etc.) for improvement of the process are thoroughly discussed. Additionally, other operations, such as trimming, curing, packaging and storage, are discussed, and the effect of the different postharvest operations on the cannabinoid yield is summarized. A critical investigation of the factors involved in each postharvest operation is indeed key for obtaining quality products and for the sustainable development of the cannabis industry.
... An extensive body of literature documents the association of cannabis use with an increased risk for a variety of acute and longterm health harms ( Cohen, Weizman, & Weinstein, 2019 ;Hall et al., 2019 ;Hoch, Friemel, & Schneider, 2019 ;Memedovich, Dowsett, Spackman, Noseworthy, & Clement, 2018 ; National Academies of Sciences Engineering and Medicine, 2017 ;World Health Organization, 2016 ). These include: acute intoxication with impaired cognitive, memory and psychomotor skills; increased involvement in motor-vehicle crashes and related injury and deaths; impaired neurocognitive and psychosocial functioning; mental health problems (e.g., psychosis and schizophrenia, depression and suicidal behaviors); cannabis use disorder/dependence; and select respiratory, reproductive, cardiovascular, gastro-intestinal conditions ( Cohen et al., 2019 ;Hall et al., 2019 ;Hoch et al., 2019 ;Memedovich et al., 2018 ;National Academies of Sciences Engineering and Medicine, 2017 ;Patel, Khan, & Hamid, 2020 ;World Health Organization, 2016 ). ...
... An extensive body of literature documents the association of cannabis use with an increased risk for a variety of acute and longterm health harms ( Cohen, Weizman, & Weinstein, 2019 ;Hall et al., 2019 ;Hoch, Friemel, & Schneider, 2019 ;Memedovich, Dowsett, Spackman, Noseworthy, & Clement, 2018 ; National Academies of Sciences Engineering and Medicine, 2017 ;World Health Organization, 2016 ). These include: acute intoxication with impaired cognitive, memory and psychomotor skills; increased involvement in motor-vehicle crashes and related injury and deaths; impaired neurocognitive and psychosocial functioning; mental health problems (e.g., psychosis and schizophrenia, depression and suicidal behaviors); cannabis use disorder/dependence; and select respiratory, reproductive, cardiovascular, gastro-intestinal conditions ( Cohen et al., 2019 ;Hall et al., 2019 ;Hoch et al., 2019 ;Memedovich et al., 2018 ;National Academies of Sciences Engineering and Medicine, 2017 ;Patel, Khan, & Hamid, 2020 ;World Health Organization, 2016 ). Some of these associations are stronger than others, and causality is not always firmly established. ...
... Moreover, definitions of intensive use have varied, but it is commonly defined as 'daily/near-daily' use. On this basis, there is substantial evidence that frequent cannabis use, also when directly compared with less frequent (e.g., occasional) use, represents and functions as a strong predictor of adverse health outcomes ( Cohen et al., 2019 ;Curran et al., 2016 ;Sagar & Gruber, 2018Steeger et al., 2021 ). ...
Article
Full-text available
Background Cannabis use is common, especially among young people, and is associated with risks for various health harms. Some jurisdictions have recently moved to legalization/regulation pursuing public health goals. Evidence-based ‘Lower Risk Cannabis Use Guidelines’ (LRCUG) and recommendations were previously developed to reduce modifiable risk factors of cannabis-related adverse health outcomes; related evidence has evolved substantially since. We aimed to review new scientific evidence and to develop comprehensively up-to-date LRCUG, including their recommendations, on this evidence basis. Methods Targeted searches for literature (since 2016) on main risk factors for cannabis-related adverse health outcomes modifiable by the user-individual were conducted. Topical areas were informed by previous LRCUG content and expanded upon current evidence. Searches preferentially focused on systematic reviews, supplemented by key individual studies. The review results were evidence-graded, topically organized and narratively summarized; recommendations were developed through an iterative scientific expert consensus development process. Results A substantial body of modifiable risk factors for cannabis use-related health harms were identified with varying evidence quality. Twelve substantive recommendation clusters and three precautionary statements were developed. In general, current evidence suggests that individuals can substantially reduce their risk for adverse health outcomes if they delay the onset of cannabis use until after adolescence, avoid the use of high-potency (THC) cannabis products and high-frequency/-intensity of use, and refrain from smoking-routes for administration. While young people are particularly vulnerable to cannabis-related harms, other sub-groups (e.g., pregnant women, drivers, older adults, those with co-morbidities) are advised to exercise particular caution with use-related risks. Legal/regulated cannabis products should be used where possible. Conclusions Cannabis use can result in adverse health outcomes, mostly among sub-groups with higher-risk use. Reducing the risk factors identified can help to reduce health harms from use. The LRCUG offer one targeted intervention component within a comprehensive public health approach for cannabis use. They require effective audience-tailoring and dissemination, regular updating as new evidence become available, and should be evaluated for their impact.
... 23,33,34 Despite the challenges to research, medical cannabis has been approved in some states as a supportive treatment for an expanded number of medical conditions. 15,16,[34][35][36][37][38][39][40][41][42] Patients are challenged to abide by the US Supreme Court which holds that state laws authorizing medical cannabis use and possession do not insulate individuals from federal law and criminalization. Changing federal policies are also challenging where they make it easier to prosecute individual users, while at the same time following state policies and clinical recommendations to use medical cannabis as a complementary treatment for certain debilitating conditions, even when there is limited evidence of long-term efficacy. ...
... There are continuous efforts to shed light on the health impact of recreational marijuana and MMJ. 34,37,38,40,42,50,51 Ghasemiesfe et al 50 ascertained in their systematic review that low-quality evidence suggests sustained marijuana use may increase the risk for testicular cancer whereas other cancers remains unclear. In another review, there was only low-quality evidence of the opioidsparing effect of cannabinoids. ...
... 38,50 Despite low-quality d mainly due to heterogeneity and small numbers of the study populations and the observational nature of most of the published evidence d and scarcity of evidence, medical cannabis has been approved in some states as a supportive treatment for an expanded number of medical conditions. 15,16,[34][35][36][37][38][39][40][41][42] Recognizing the growing usage of medical cannabis, health care entities have had to adopt policies and procedures to address patients' desire for medical cannabis use during hospitalization while navigating the complicated regulatory landscape (Table). ...
Article
Full-text available
Thirty-six states and four territories in the United States have legalized cannabis for medical and/or recreational use. Marijuana, however, continues to be classified as a schedule I substance under the Federal Controlled Substance Act and remains illegal under US federal law. The incongruity between state and federal legislation creates various challenges for stakeholders: patients, medical trainees, providers, and health care institutions. This communication provides an overview of the major policies impacting Cannabis sativa use within the United States, various state and federal regulations, and highlights potential implications for health care institutions moving forward. Existing literature, regulations, and policies on medical marijuana (MMJ) use in health care settings were searched, reviewed, analyzed, and distilled. As a consequence of legislative inconsistencies, there is insufficient clarity and resultant challenges regarding MMJ usage, prescription, possession, education, and research-related policies for health care stakeholders across the United States. Coupled with limited scientific evidence on the clinical efficacy of MMJ, the needs of the patient and the quality of health care delivery may be affected as hospitals balance the competing risks of being legislatively compliant while protecting the rights of patients and health care employees. There is a recognized need to better define acceptable MMJ policies and regulations in health care settings that are evidence-based, legally compliant, and adequately address the needs of both patients and providers. Given the complexity of the legal and policy landscape, there are potential opportunities for improvement, including in medical education and training, research, and usage oversight of MMJ for stakeholders in the United States.
... Epidemiological evidence has linked lung disease, increased respiratory and cardiovascular symptoms, chronic bronchitis and chronic obstructive disease and emphysema to marijuana smoking [33]. In some instances, marijuana use can cause alteration and sometimes loss in memory characterized by slowed reaction time, hampered information processing, un-coordinated motor reactions and performance, and attention deficiency that result in mood disorder syndrome, psychosis and schizophrenia [34]. Accordingly, a review on the effects of marijuana smoking on the lungs found out that prolonged cannabis smoking leads to lung cancer and cancers of the upper aero digestive tract [35]. ...
... The endocannabinoid system receptors, cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2) offer inhibitory function, where CB1 receptor act on the production of cyclic adenosine monophosphate pathway once they receive a signal from adenyl cyclase inhibitor activation while CB2 receptor plays an important role in blocking inflammatory activity and tissue damage [1]. Therefore, brain structural abnormality has been observed in chronic cannabis smokers with more effects imposed on the grey and white matter density [34]. Moreover, variable brain activity among cannabis consumers has been reported and compared to non-smokers in which greater brain activation is observed in the prefrontal region of smokers while hypo-activation is noted along the left superior parietal cortex due to high concentrations of the two cannabinoids, THC and CBD, THC alters the hippocampal capacity and neurochemistry while on the other hand, CBD defends against toxic variations [40]. ...
... Pharmacological and toxicological properties of cannabis are contributed by eighteen classes of chemicals which include hydrocarbons, sugars, simple fatty acids, terpenes, amino acids, and nitrogenous compounds [43]. Accordingly, cannabis has been used for treating oncology patients [44], epileptic patients [45], and management of inflammatory bowel disease [46], neurological and psychiatric disorders [34], and sometimes in children to treat autism spectrum disorder, fetal alcohol spectrum disorder and in pregnant mothers in the management of hyperemis gravidarum [7]. This has been attributed to the non-psychoactive cannabinoid CBD which interacts with the CB2 receptor that gets activated to reduce pain, seizures and inflammations in patients, and sometimes in the management of epilepsy, schizophrenia and post-traumatic stress disorders [1]. ...
... In turn, the CB2 receptor is mostly found in peripheral cells of the immune system [20] (p. 1140) such as the spleen, tonsils, and thymus [16] (p. ...
... Another complex pathology that benefits from the bioactivity of these compounds are multiple sclerosis, which is an autoimmune disease characterized by demyelination that occurs in CNS [20] (p. 1143), leading to characteristic symptoms such as spasticity that causes severe pain and difficulty sleeping [31] (p. ...
... It also can activate CB1 receptors, suspending the emetic effects triggered by serotonin and dopamine [31] (pp. [19][20]. THC has the ability to stimulate appetite through the activation of CB1 receptors located at the level of the hypothalamus and which are responsible for regulating the energy balance ( [32,34] (pp. ...
Article
Full-text available
Translational research made with Cannabis sativa L. and its biocompounds provides data for some targeted diseases, as also symptoms associated with Autism Spectrum Disorders (ASDs). The main compounds ∆9-tetrahydrocannabinol (THC) and cannabidiol (CBD), are capable of modulating the endocannabinoid system since its dysregulation interferes with the pathophysiology of ASDs there are clinical evidence for its potential use in the treatment of the disease. Conventional therapy still has limitations, as it does not always treat the central symptoms, and there are many patients who do not respond to treatment, which demands more research on new therapies. Through the analysis of published literature on this topic, it is verified that cannabinoids, in particular CBD, improves symptoms associated with common comorbidities in ASDs. Some studies also demonstrate the therapeutic potential of these compounds in the treatment of central symptoms of autism. In addition, cannabinoid therapy to ASDs is associated with low adverse effects and a reduction in concomitant medication. Although it appears to be promising, it is essential to do the translation of this data into clinical research and some of its potential and critical gaps are discussed in this review pointing to large-scale and long-term clinical trials that should include more patients and homogeneous samples.
... Cannabis is the generic name used to refer to psychoactive substances obtained from the Cannabis sativa female plant, known as cannabinoids [39]. Overall, a cannabinoid is an organic compound belonging to the group of terpenophenolics, which can activate the cannabinoid receptors of humans. ...
... Other cannabinoids present in the Cannabis sativa plant with a lower psychoactive potency are cannabidiol (CBD) and delta-8-tetrahydrocannabinol. In particular, CBD is a cannabinoid that is not currently considered to be psychoactive or, at least, not addictive [27,39,41]. In fact, while THC acutely impairs learning and can produce psychosis-like effects and increase anxiety, CBD can enhance learning and seems to have antipsychotic and anti-anxiety properties in humans [41]. ...
... Acute cannabinoid use induces changes in brain neurochemistry, such as an increased dopamine release, reduced glutamatergic transmission, the release of endogenous opioids and the inhibition of acetylcholine secretion [39]. These brain biochemical changes are responsible for the acute effects of cannabis, which can be divided into physiological, psychological or behavioral and cognitive effects [42,46]. ...
Article
Full-text available
Gender differences in psychiatric disorders and drug use are well known. Cannabis is the most widely used illegal drug among young people. In recent years, its use has been related to the development of psychiatric pathologies; however, few studies have incorporated the gender perspective as of yet. The present work analyses the literature to determine the existence of gender differences in the development of psychotic, depressive and anxious symptoms associated with cannabis use. First, we describe cannabis misuse and its consequences, paying special attention to adolescent subjects. Second, the main gender differences in psychiatric disorders, such as psychosis, depression, anxiety and cannabis use disorders, are enumerated. Subsequently, we discuss the studies that have evaluated gender differences in the association between cannabis use and the appearance of psychotic, depressive and anxious symptoms; moreover, we consider the possible explanations for the identified gender differences. In conclusion, the studies referred to in this review reveal the existence of gender differences in psychiatric symptoms associated with cannabis use, although the direction of such differences is not always clear. Future research is necessary to discern the causal relationship between cannabis use and the development of psychiatric symptoms, as well as the gender differences found.
... 1,2 Cannabinoids refer to all ligands of the cannabinoid receptors, that is, the G-protein coupled AU4 c CB1 and CB2-receptors, and include phytocannabinoids, synthetic cannabinoid analogs, and endogenous ligands (endocannabinoids), such as some ethanolamides, anandamide, and 2arachidonoylglycerol. 1,3 In Western countries, the use of cannabis preparations for recreational and medical purposes is prevalent and increasing, also with regard to medical cannabis. 1,4,5 Therefore, knowing the consequences of cannabis use on body and brain is essential. ...
... Meanwhile, we know a lot about the risks and benefits of cannabis use for mammalian and human behavior as well as for several brain functions. [1][2][3][4] While we have some information about the impact of cannabis on the heart, lung, concerning the influence of cannabis on human renal function. 1,6,7 However, experimental data suggest that cannabis and cannabinoids could exert both, harmful and beneficial effects on kidney. ...
Article
Introduction: Human studies about the impact of cannabis use on both healthy kidneys as well as kidney function in patients with kidney disease are lacking. To shed more light on this understudied topic, we reevaluated a previous clinical study. The sample of this study was exclusively suited for investigating effects of recreational long-term cannabis use on humans under real-life conditions. Methods: This special sample had sought and was undergoing inpatient detox-treatment. It was characterized by a lone and considerable cannabis-dependence without any other relevant active comorbidity (except of a concurrent nicotine-dependence). In the present post hoc analysis, we are focused on this sample's routine laboratory tests at admission, including the glomerular filtration rate (GFR), which is the key routine parameter for kidney function assessment. Next, we investigated the association between participants' GFR and their cannabis-related data, including serum cannabinoid levels (Δ-9-tetrahydrocannabinol and main metabolites 11-Hydroxy-Δ-9-tetrahydrocannabinol and 11-Nor-9-carboxy-Δ-9-tetrahydrocannabinol). Results: In the whole sample (N=42; 9 females; mean 28.7 years old), we found five persons (12%; 95% confidence interval [2.1-21.7%]) with a mild kidney dysfunction (GFR; 86-75 mL/min). These persons (two females), however, had reported a stronger nicotine misuse. Furthermore, we found no significant association between the study-populations' GFR and reported cannabis burden (median daily use 2.5 g for 36 months, moderate general symptom-load). Most remarkably, the GFR was also not significantly correlated with the serum cannabinoid-levels. Conclusion: Chronic recreational cannabis-use (including its related discomfort) did not affect the kidney function of our almost selectively "cannabis-burdened" population in a relevant manner.
... Cannabinoids possess high therapeutic potential, particularly in the management of pain (Donvito et al., 2018), by acting on their main target, the cannabinoid type-1 (CB 1 ) receptor (Cohen et al., 2019). However, because of significant side effects (e.g., cognitive and motor dysfunctions; Borgelt et al., 2013;Prashad and Filbey, 2017) their medical and recreational use is under intense scrutiny (Cohen et al., 2019). ...
... Cannabinoids possess high therapeutic potential, particularly in the management of pain (Donvito et al., 2018), by acting on their main target, the cannabinoid type-1 (CB 1 ) receptor (Cohen et al., 2019). However, because of significant side effects (e.g., cognitive and motor dysfunctions; Borgelt et al., 2013;Prashad and Filbey, 2017) their medical and recreational use is under intense scrutiny (Cohen et al., 2019). In particular, the activation of CB 1 receptors impairs motor control (Giuffrida and Seillier, 2012;Monory et al., 2007), and cataleptic-like effects are considered the leading cause of vehicle accidents induced by human cannabis consumption (Martin et al., 2017). ...
Article
Recent advances in neuroscience have positioned brain circuits as key units in controlling behavior, implying that their positive or negative modulation necessarily leads to specific behavioral outcomes. However, emerging evidence suggests that the activation or inhibition of specific brain circuits can actually produce multimodal behavioral outcomes. This study shows that activation of a receptor at different subcellular locations in the same neuronal circuit can determine distinct behaviors. Pharmacological activation of type 1 cannabinoid (CB1) receptors in the striatonigral circuit elicits both antinociception and catalepsy in mice. The decrease in nociception depends on the activation of plasma membrane-residing CB1 receptors (pmCB1), leading to the inhibition of cytosolic PKA activity and substance P release. By contrast, mitochondrial-associated CB1 receptors (mtCB1) located at the same terminals mediate cannabinoid-induced catalepsy through the decrease in intra-mitochondrial PKA-dependent cellular respiration and synaptic transmission. Thus, subcellular-specific CB1 receptor signaling within striatonigral circuits determines multimodal control of behavior.
... This association agrees with previous studies and is relevant to both cannabinoid abuse and the abuse of other illicit drugs (Krebs et al. 2019). Studies have also documented that, compared to cannabinoids, the abuse of SCs (Strox and voodoo) is associated with more serious and long-lasting psychiatric illnesses (Cohen et al. 2019). Furthermore, amphetamine was reported to be associated with violence, aggression, schizophrenia, obsession, and paranoid thinking (Zweben et al. 2004). ...
... Apart from cannabinoids-associated psychiatric illnesses, the injurious effects of cannabinoids include other health disorders. Airway disease, lung cancer, increased cardiovascular activity, acute myocardial infarction, sudden arrest, and cardiomyopathy are all associated with cannabinoid use (Cohen et al. 2019). In addition to lung cancer, in vitro studies have mentioned that cannabinoids modulate the immune system and disturb the T helper cell and cytokines expression, which might induce carcinogenesis in the head and neck as well as other organs (Tanasescu and Constantinescu 2010). ...
Article
Full-text available
Global surveys have highlighted rise in consumption of cannabinoids among residents of both developed and developing countries. Cannabinoids cause severe damage to the cardiovascular, nervous, respiratory, and renal systems, and have been linked with several deaths. Despite these adverse health effects, the use of cannabinoids has rapidly increased. This work seeks to estimate the prevalence of cannabinoid abuse among Egyptian university students and explore the associated risk factors. A cross-sectional study was carried out over 3 months (1st of July–1st of October 2020) and included 2380 students. Participants were subjected to a pre-designed self-administered questionnaire that included demographic data, Addiction Severity Index, and Depression Anxiety Stress Scale. Among the participating students, 4.9% of them reported cannabinoid abuse and 41% reported smoking cigarettes. The most used substances were hashish (96.5%), Strox (41.3%), Bhang (34.4%), voodoo (34.4%), and Tramadol (31.1%). Gender and social status were also significantly related to rates of substances abuse; most illicit drug users were males (93.1%), and the majority was of low (41.3%) or moderate (50.8%) socioeconomic status. The most significant risk factors associated with substance use were positive history of family conflict (OR=6.48; CI95%: 5.08–8.64, p<0.001), encouragement by peers (OR=2.95; CI95%: 1.73–5.05, p<0.001), male gender (OR=5.46; CI95%: 2.40–12.44, p=0.001), positive history of child abuse (OR=2.85; CI95%: 1.96–3.04, p=0.001), having a stay-at-home mother (OR= 1.56, CI95%: 1.19–2.04, p=0.001), living in an urban area (OR=2.22; CI95%: 1.53–5.0, p=0.002), and positive family history of substance use (OR=1.98; CI95%: 1.48–2.08, p=0.045). This study emphasizes the possible significant rise in substance use among university students. Awareness campaigns should target both students and student families.
... C. sativa L. is used by approximately 3% of the global population as a relaxant (United Nations Office on Drugs and Crime, 2017). Tetrahydrocannabinol (THC) and cannabidiol (CBD) are the major constituents of cannabis, known as cannabinoids, and both exhibit neurological and psychiatric activities (Cohen et al., 2019;Friedman et al., 2019). ...
... Cannabis species contain 110 cannabinoids and 440 noncannabinoid compounds, including terpenoids, flavonoids, and sterols (Solymosi and Köfalvi, 2017). Therapeutic studies suggest that cannabis is clinically useful for the treatment of a wide range of pathological conditions, including neurological and psychiatric disorders (Cohen et al., 2019;Friedman et al., 2019). The major cannabinoids of cannabis include CBD, THC, cannabinol, and cannabichromene ( Figure 1). ...
Article
Full-text available
Cannabis sativa L. is an annual herb oldest cultivated plants as a source of fiber since about 5000 B.C. On the other hand, the cannabis flower and seed are listed in Shennong’s classic Materia Medica approximately 2000 years ago. The formulas prescribed with cannabis in Kampo medicine have been summarized. Cannabidiol (CBD) and tetrahydrocannabinol (THC) are the major neurological and psychiatric cannabinoids, and develop to drugs. It becomes evident that the therapeutic CBD and/or THC are the important candidate of anti-dementia drugs having different mechanism for Alzheimer’s patients. Two receptors and endocannabinoids are also discussed for underlying mechanism of action. In order to promote the breeding of cannabis plant containing higher concentration of target cannabinoid the biosynthetic enzymes were isolated, cloning and the tertiary structure of THCA synthase determined by x-ray analysis resulting in the possibility of molecular breeding for cannabinoids.
... The legalization of cannabis in multiple regions of the USA -36 and 15 states have now legalized medical marijuana and recreational marijuana, respectively -raises concerns about its potential hazard to health. Research into the therapeutic potential of cannabinoid-based drugs suggests that they are clinically useful in a wide range of pathological conditions, including neurological 4 and psychiatric disorders 5 . However, repeated recreational and medical cannabis use has been associated with short-term and long-term side effects, including respiratory and cardiovascular disorders, cognitive alterations, psychosis, schizophrenia and mood disorders 5 . ...
... Research into the therapeutic potential of cannabinoid-based drugs suggests that they are clinically useful in a wide range of pathological conditions, including neurological 4 and psychiatric disorders 5 . However, repeated recreational and medical cannabis use has been associated with short-term and long-term side effects, including respiratory and cardiovascular disorders, cognitive alterations, psychosis, schizophrenia and mood disorders 5 . In the past 5 years, an unfavourable effect on male reproductive health has also been claimed 6,7 . ...
Article
Marijuana is the most widely consumed recreational drug worldwide, which raises concerns for its potential effects on fertility. Many aspects of human male reproduction can be modulated by cannabis-derived extracts (cannabinoids) and their endogenous counterparts, known as endocannabinoids (eCBs). These latter molecules act as critical signals in a variety of physiological processes through receptors, enzymes and transporters collectively termed the endocannabinoid system (ECS). Increasing evidence suggests a role for eCBs, as well as cannabinoids, in various aspects of male sexual and reproductive health. Although preclinical studies have clearly shown that ECS is involved in negative modulation of testosterone secretion by acting both at central and testicular levels in animal models, the effect of in vivo exposure to cannabinoids on spermatogenesis remains a matter of debate. Furthermore, inconclusive clinical evidence does not seem to support the notion that plant-derived cannabinoids have harmful effects on human sexual and reproductive health. An improved understanding of the complex crosstalk between cannabinoids and eCBs is required before targeting of ECS for modulation of human fertility becomes a reality.
... Research suggests a therapeutic potential of cannabis for relieving symptoms of some health conditions, including neuropathic pain (Cohen et al., 2019). However, long-term or heavy cannabis use is associated with the development of chronic health conditions such as respiratory function decline and cardiovascular disease Degenhardt, 2009, 2014;Tashkin, 2013;Thomas et al., 2014). ...
Article
Background Despite significant geographical heterogeneity of sociodemographic and clinical characteristics, little is known about potential differences in cannabis use behaviors in U.S. geographic areas. In this study, we examined cannabis use behaviors in large metropolitan, small metropolitan, and nonmetropolitan areas. We focused on interactions between geographic areas and health insurance status and medical cannabis laws (MCL). Methods Data came from the 2015-2018 National Survey on Drug Use and Health (NSDUH; N = 171,766 adults; N = 36,175 marijuana users). Weighted chi-squares tests of independence and multivariable Poisson regression models were used to examine study questions. Results Past-year use was highest in large metropolitan areas (16.08%). Frequent use was highest among nonmetropolitan area users (48.67%). Uninsured adults had a higher likelihood of past-year use (RRR = 1.21, 95% CI = 1.14, 1.29) and frequent use (RRR = 1.27, 95% CI = 1.14, 1.41), but a lower likelihood of cannabis use disorder (RRR = 0.77, 95% CI = 0.66, 0.89). Uninsured adults in nonmetropolitan areas had a higher likelihood (RRR = 1.62, 95% CI = 1.39, 1.88) of past-year use than insured nonmetropolitan area adults. MCL state residency was associated with a higher likelihood of frequent use among nonmetropolitan (RRR = 1.39, 95% CI = 1.11, 1.74) and small metropolitan users (RRR = 1.30, 95% CI = 1.15, 1.47). Cannabis use disorder likelihood did not vary by geographic area. Conclusions Lack of health insurance and MCL state residency are significant variables affecting cannabis use behaviors in small metropolitan and/or nonmetropolitan areas.
... The recent findings suggest that possibly relevant mechanisms of CBD encompass the facilitation of serotonergic neurotransmission via allosteric 5-HT 1 A receptor modulation, modulation of glucose homeostasis and inflammatory processes by PPARγ activation, and the interaction with the transient receptor potential vanilloid-1 receptor (TRPV1) (22,23). Recent evidence suggests the therapeutic potential of cannabinoidbased drugs for a wide range of medical conditions, including neurological and psychiatric disorders (24). ...
Article
Full-text available
There is an increasing interest in cannabis use in neuropsychiatry. The evidence is relatively scarce or of low quality or comes from the pre-clinical research. Nevertheless, it supports the endocannabinoid system’s role in regulating stress, mood, cognitive abilities, and sleep. The effects such as euphoric, anxiolytic, calming, or sleep-inducing are well known from recreational use experiences. There is increasing evidence for cannabinoids in the therapeutic use for anxiety, depression, insomnia, psychoses, and opioid substitution. In this mini-review, we tried to signal the research’s key directions on cannabis in psychiatry. Where possible, we presented the clinical evidence to provide an overview of the state of knowledge. We avoided too detailed explanation of the pathophysiology or etiology, bearing in mind that the special issue “The Endocannabinoid System: Filling the Translational Gap between Neuroscience and Psychiatry” will consist of translational research articles and problem-specific papers. We hope that the article will be a kind of roadmap of the prospects of current and research.
... CB1 receptors are located mainly in neurons of the central and peripheral nervous system [4]. The primary effect of cannabinoids in these receptors is the inhibition of synaptic transmission, which causes changes of mood and perception, such as pain sensation, sleep, body temperature or food intake [5]. Cannabinoids also target CB2 receptors, located in tissues of the immune system. ...
Article
Full-text available
Synthetic cannabinoids (SCs) are one of the most frequent classes of new psychoactive substances monitored by the EU Early Warning System and World Health Organization. UR-144 is a SC with a relative low affinity for the CB1 receptor with respect to that for the CB2 receptor. As with other cannabinoid receptor agonists, it has been monitored by the EU Early Warning System since 2012 for severe adverse effects on consumers. Since data for UR-144 human pharmacology are very limited, an observational study was carried out to evaluate its acute pharmacological effects following its administration using a cannabis joint as term of comparison. Disposition of UR-144 and delta-9-tetrahydrocannibinol (THC) was investigated in oral fluid. Sixteen volunteers smoked a joint prepared with tobacco and 1 or 1.5 mg dose of UR-144 (n = 8) or cannabis flowering tops containing 10 or 20 mg THC (n = 8). Physiological variables including systolic and diastolic blood pressure, heart rate and cutaneous temperature were measured. A set of Visual Analog Scales (VAS), the Addiction Research Centre Inventory (ARCI)-49-item short form version and the Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) were administered to evaluate subjective effects. Oral fluid was collected at baseline, 10, 20, 40 min and 1, 2, 3 and 4 h after smoking, for UR-144 or THC concentration monitoring. Results showed significant statistical increases in both systolic and diastolic blood pressure and heart rate after both UR-144 and cannabis smoking. Both substances produced an increase in VAS related to stimulant-like and high effects, but scores were significantly higher after cannabis administration. No hallucinogenic effects were observed. Maximal oral fluid UR-144 and THC concentrations appeared at 20 and 10 min after smoking, respectively. The presence of UR-144 in oral fluid constitutes a non-invasive biomarker of SC consumption. The results of this observational study provide valuable preliminary data of the pharmacological effects of UR-144, showing a similar profile of cardiovascular effects in comparison with THC but lower intensity of subjective effects. Our results have to be confirmed by research in a larger sample to extensively clarify pharmacological effects and the health risk profile of UR-144.
... In addition to acute or long-term adverse effects on neurocognitive mechanisms in the brain and executive functioning (Hasin 2018, Cohen et al. 2019, cannabis or cannabisderived product use/misuse can lead to cannabis dependence/use disorder, cardiovascular and gastrointestinal problems, seizures, hyperemesis, intoxication, urinary tract infection, psychotic symptoms, severe dysphoric reactions, and suicidal ideation (M€ ucke et al. 2018, Hall et al. 2019, Monte et al. 2019, Pratt et al. 2019, Rezkalla and Kloner 2019, Bass and Linz 2020, Page et al. 2020. Gastrointestinal problems were more common when cannabis-based medicines were administered via oral/oromucosal routes than by inhalation (Aviram and Samuelly-Leichtag 2017). ...
Article
Increasing numbers of older adults use cannabis and cannabis-derived products that can have adverse effects. This study examined management site and level of healthcare services for older adult poison control center cases involving cannabis products. Using the American Association of Poison Control Centers’ (PCC) National Poison Data System, 2016–2019, we extracted the 3109 cases aged 50+ for which cannabis was the only or primary substance. Multinomial logistic regression models were fit to examine associations between specific cannabis forms and management/care site (on site [mostly at home], at a healthcare facility [HCF], or no follow-up due to referral refusal or leaving against medical advice) and level of healthcare services for cases managed at a HCF. The results show that between 2016 and 2019, PCC cannabis cases involving older adults increased twofold, largely due to cases of cannabidiol, edibles, and concentrated extracts. Plant form and synthetic cannabinoid cases declined substantially. Compared to plant forms, synthetic cannabinoid cases had 4.22 (95% CI = 2.59–6.89) greater odds of being managed at, rather than outside, a HCF and 2.17 (1.42–3.31) greater odds of critical care unit admission. Although e-cigarette cases, compared to plant form cases, had lower odds of being managed at a HCF, HCF-managed e-cigarette cases had 3.43 greater odds (95% CI = 1.08–10.88) of critical care unit admission. Synthetic cannabinoid cases also had 1.86 (95% CI = 1.03–3.35) greater odds of no follow-up, and the presence of a secondary substance was also a significant factor. Stricter regulations for listing chemical ingredients and providing safety guidelines are needed for cannabis-derived products.
... Third, the finding that a significant proportion of medical and nonmedical users obtained cannabis via private/informal sources indicates that they are likely to use cannabis and cannabis products with unknown Δ 9tetrahydrocannabinol (THC) potency. Given the increase in THC potency (37)(38)(39)(40)(41), healthcare professionals should educate older cannabis users, especially high-frequency users, on potential safety issues and adverse health effects of cannabis and cannabis products obtained from unregulated sources. With growing numbers of states legalizing cannabis, further examination of sources and user behaviors related to obtaining nonmedical and medical cannabis is needed to better monitor safety issues and other adverse health effects. ...
Article
Background: US epidemiologic data show that nearly one in 10 individuals aged 50+ report past-year cannabis use, and nearly one in five users report medical use. However, research on older cannabis users, especially medical cannabis users, is scant. Objectives: We examined medical and nonmedical cannabis users aged 50+ on health-related characteristics, cannabis use patterns, and cannabis sources. Hypotheses were that compared to nonmedical users, medical users are more likely to have physical and mental health problems, use healthcare services, discuss their drug use with a healthcare professional, use cannabis more frequently, and purchase cannabis from a medical dispensary and other sources rather than obtain it as a gift, share someone else’s, or use other means. Methods: We used 2018 and 2019 National Survey on Drug Use and Health data (N = 17,685 aged 50+; male = 8,030; female = 9,655). Hypotheses were tested using logistic regression analysis. Results: The past-year cannabis use rate was 8.9%. Of past-year users, 18.5% reported medical use. Compared to nonmedical use, medical use was associated with lower odds of alcohol use disorder but higher odds of discussing drug use with a healthcare professional (AOR = 4.18, 95% CI = 2.53–6.89), high-frequency use (e.g., AOR = 2.56, 95% CI = 1.35–4.86 for 200–365 days), and purchase at a medical cannabis dispensary (AOR = 4.38, 95% CI = 2.47–7.76). Conclusion: Medical and nonmedical users did not differ on physical and most behavioral health indicators. Most obtained cannabis from private/informal sources. Some medical users are likely to self-treat without healthcare professional consultation. Healthcare professionals should engage older adults in discussions of cannabis use and behavioral health needs.
... With the above compiled data and studies over the use and wonders of medical cannabis in various disorders, it becomes equally necessary to look though why this drug got illegal in the first place and what the possible and unwanted side effects that it pose. Major adverse effects of cannabis use were found to be on nervous system and psychiatric health, respiratory system, and cardiovascular system [127]. It is noticed that there is an increased risk of psychiatric disorder on vulnerable population and naïve users post-cannabis use, with anxiety and panic attack in naïve users [128,129]. ...
Article
Full-text available
i>Cannabis sativa L. is an annual herbaceous dioecious plant which was first cultivated by agricultural human societies in Asia. Over the period of time, various parts of the plant like leaf, flower, and seed were used for recreational as well as therapeutic purposes. The main chemical components of Cannabis sativa are termed as cannabinoids, among them the key psychoactive constituent is Δ-9-tetrahydrocannabinol and cannabidiol (CBD) as active nonpsychotic constituent. Upon doing extensive literature review, it was found that cannabis has been widely studied for a number of disorders. Very recently, a pure CBD formulation, named Epidiolex, got a green flag from both United States Food and Drug Administration and Drug Enforcement Administration for 2 rare types of epilepsies. This laid a milestone in medical cannabis research. This review intends to give a basic and extensive assessment, from past till present, of the ethnological, plant, chemical, pharmacological, and legal aspects of C. sativa . Further, this review contemplates the evidence the studies obtained of cannabis components on Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis, multiple sclerosis, emesis, epilepsy, chronic pain, and cancer as a cytotoxic agent as well as a palliative therapy. The assessment in this study was done by reviewing in extensive details from studies on historical importance, ethnopharmacological aspects, and legal grounds of C. sativa from extensive literature available on the scientific databases, with a vision for elevating further pharmaceutical research to investigate its total potential as a therapeutic agent.
... 41,42 The main side effects from cannabis products are due to the effects of THC, and these effects are amplified when consumed via methods with quicker absorption such as smoking or vaping compared with oral ingestion. 43 Moreover, the pharmacokinetics and pharmacodynamics differ between inhalation and oral ingestion influencing the onset and duration of desired AEs for each method of administration. 44 Given the greater frequency of side effects associated with inhalation, as identified in this review, some FMS patients may prefer other forms of administration. ...
Article
Background: Fibromyalgia (FMS) is a complex condition that is characterized by various pain syndromes and fatigue, among other symptoms experienced. Current medical treatment of FMS involves both pharmacological and nonpharmacological approaches, but often with ineffective outcomes. Medicinal cannabis has the potential to be a therapeutic option for patients with FMS due to the positive research in chronic pain management. In addition, it has been found to have fewer adverse effects compared with currently available pain medications. This literature review aims at answering whether medicinal cannabis is reported to be safe and effective for the treatment of pain and symptomology experienced by people with FMS. Methods: A systematic review was conducted on human trials utilizing cannabis in FMS. MEDLINE, Embase, CINAHL, AMED, Scopus, and Cochrane CENTRAL were used for databases search, and mesh terms were used for cannabis and FMS. The search was limited to studies conducted from 2000 to 2020. Results: From the 181 citations identified, 10 studies were included after title, abstract, and full text screening occurred. A total of 1136 of patients (intervention n = 945, control n = 108, crossover n = 83) participated in the 10 studies ranging from 9 to 383 patients (mean = 114, median = 36). Of these studies, there were three randomized controlled trials, six observational studies, and one study that compared the management of chronic pain patients with FMS patients. Cannabis was found to be safe and well tolerated in FMS. The main adverse events identified included feeling ‘‘high,’’ dizziness/vertigo, dry mouth, cough, red eyes, and drowsiness with no serious adverse events reported. Conclusions: This literature review identified that medical cannabis may be beneficial for some people with FMS. Further studies are required to confirm its efficacy, what type of cannabis is the most effective form to use, and what assessment tools need to be utilized to understand how to quantify clinical outcomes.
... [2][3][4][5] No obstante este escenario, su uso se ha asociado con problemas cardiorrespiratorios, alteraciones cognitivas, psicosis y esquizofrenia, entre otros. 6 Por tal motivo, es necesario continuar estudiando los posibles efectos terapéuticos de la cannabis, a fin de conocer sus alcances y limitaciones dentro del campo médico; de hecho, varios investigadores de todo el mundo debaten fuertemente acerca de su uso debido a las complicaciones que se pueden presentar durante y después de su consumo. Aunado a esto, para algunas enfermedades su uso solo está considerado como un tratamiento complementario, mientras que para otras su uso está contraindicado. 1 La capacitación y formación de médicos de licenciatura y posgrado que se está otorgando respecto al uso de la cannabis no está a la par de la actualización de las alternativas terapéuticas existentes, esto puede crear una brecha de desinformación que crea una limitante para los médicos en cuanto a estas y otras opciones de tratamiento. ...
Article
Full-text available
p> Objetivo: identificar el nivel de conocimiento sobre los usos terapéuticos de la cannabis en personal médico adscrito a un hospital del Estado de México . Métodos: estudio transversal. Se elaboró un instrumento de once preguntas para identificar el nivel de conocimiento sobre los usos terapéuticos de la Cannabis sativa e indica . El instrumento clasificó el conocimiento en suficiente, medianamente suficiente y no suficiente; participaron 31 médicos generales y especialistas; se realizó estadística descriptiva para el análisis de los resultados obtenidos. Resultados: 71% de los participantes era del sexo masculino (22) y 29%, femenino (9); 25% tenía estudios de licenciatura (8) y 74% había cursado una especialidad (23). Al evaluar el nivel de conocimiento acerca de los usos terapéuticos de cannabis se encontró que 71% de los médicos tenía un nivel de conocimiento medianamente suficiente (22), 16.1%, conocimiento suficiente (5) y 12.9%, no suficiente (4). Conclusiones: la mayoría de los entrevistados tuvo un nivel de conocimientos medianamente suficiente. Es importante realizar más estudios sobre el uso terapéutico del cannabis, realizar un análisis crítico de la evidencia sobre este tópico y mejorar la capacitación y actualización sobre posibles alternativas terapéuticas en médicos generales y especialistas.</p
... In addition, they have much higher efficacy and affinity to bind to cannabinoid receptors as compared to the natural forms. Their appeal is further enhanced to the younger demographic, as they are also challenging to identify with routine drug screenings [5]. ...
Article
Full-text available
Objectives To explore the independent association between cannabis abuse and subsequent hospitalizations for acute pancreatitis (AP) and delineate the demographic differences among AP in patients with and without persistent cannabis abuse. Methods We conducted a retrospective cross-sectional study using the nationwide inpatient sample and included 50,444,133 patients (age 18-50 years) with a primary discharge diagnosis for medical illnesses and further grouped by presence of AP (N = 666,248). We used the logistic regression model to measure the odds ratio (OR) of the association between cannabis abuse and hospitalization for AP and adjusted it for demographic confounders and comorbid risk factors. Results Cannabis abuse significantly increases the odds for AP-related hospitalization (OR 2.12, P <0.001). When the regression model was controlled for potential risk factors (gall stones, cystic fibrosis, hypertriglyceridemia, hypercalcemia, hyperparathyroidism, abdominal surgeries, tobacco abuse, and alcohol abuse), cannabis abuse did not increase the odds for AP-related hospitalization (OR 0.72, P <0.001) due to the significant effect caused by gallstones (OR 30.98, P <0.001) and alcohol abuse (OR 12.69, P <0.001). AP inpatients with cannabis abuse were younger compared to non-cannabis abusers (mean age, 35.7 vs. 37.9 years), and majorly male (70.9% vs. 53.8%). AP was considerably more prevalent in whites (60.6%), followed by blacks (18.3%) and Hispanics (15.2%). Conclusion Cannabis abuse increased the unadjusted odds for AP-related hospitalization by two times, but after controlling for potential risk factors the adjusted odds of association significantly reduced. Cannabis-induced AP can be treated if a problematic recreational cannabis use pattern is discontinued at an earlier stage. Therefore, awareness campaigns and early supportive therapy among cannabis abusers might help diagnose and treat the comorbidity and improve the quality of life.
... In recent years, there has been a global shift in perspectives on the utility of cannabis. While cannabis has predominantly been associated with recreational and/or problematic use, the plant or its components, cannabinoids, are increasingly regarded as a viable treatment option for medical conditions, such as chronic pain, spasticity, nausea, and epilepsy [1], and as a potential treatment of other conditions [2][3][4]. ...
Article
Full-text available
Background The use of cannabis as medicine (CaM) both prescribed and non-prescribed has increased markedly in the last decade, mirrored in a global shift in cannabis policy towards a more permissive stance. There is some evidence that cannabis functions as a substitute for prescription drugs, particularly opioids; however, more knowledge is needed on the motives of substitution users, their patterns of use, and perceived effects of substitution use. Aims To explore who substitutes prescription drugs with cannabis, the type of prescription drugs substituted and the type of cannabis used, and the impact that substitution with cannabis has on prescription drug use as well as the motives for substitution in terms of experienced effects and side effects. Methods A self-selected convenience sample was recruited through social media, public media, and patient organizations to take part in an anonymous online survey. Inclusion criteria were 18 years or older and use of cannabis (prescribed or non-prescribed) with a medical purpose. Results The final sample included 2.841 respondents of which the majority (91%) used non-prescribed cannabis, and more than half (54.6%) had used CaM with the purpose of replacing a prescribed drug. Compared to non-substitution users, substitution users were more likely to be women and to use CaM in the treatment of chronic pain and other somatic conditions. Pain medication (67.2%), antidepressants (24.5%), and arthritis medication (20.7%) were the most common types of drugs replaced with CaM. Among substitution users, 38.1% reported termination of prescription drug use, and 45.9% a substantial decrease in prescription drug use. The most frequent type of cannabis used as a substitute was CBD-oil (65.2%), followed by ‘hash, pot or skunk’ (36.6%). More than half (65.8%) found CaM much more effective compared to prescription drugs, and 85.5% that the side effects associated with prescription drug use were much worse compared to use of CaM. Conclusion CaM is frequently used as a substitute for prescription drugs, particularly opioids. More research is needed on the long-term consequences of use of CaM, including the impact from low and high THC cannabis products on specific somatic and mental health conditions.
... For the pregnant or lactating person, negative health effects remain the same within and outside of pregnancy; harms include respiratory and cardiovascular disorders as well as mental health and addiction challenges [22][23][24][25][26][27] . There is evidence that pregnant cannabis users are at greater risk for anemia than non-pregnant users 28 . ...
Preprint
Full-text available
Background: Cannabis use during the perinatal period is rising. Objectives: To synthesize existing knowledge on the perspectives of pregnant people and their partners about cannabis use in pregnancy and lactation. Search strategy: We searched MEDLINE, APA PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Social Science Citation Index, Social Work Abstracts, ProQuest Sociology Collection up until April 1, 2020. Selection criteria: Eligible studies were those of any methodology which included the perspectives and experiences of pregnant or lactating people and their partners on cannabis use during pregnancy or lactation, with no time or geographical limit. Data collection and analysis: We employed a convergent integrative approach to the analysis of findings from all studies, using Sandelowski’s technique of “qualitizing statements” to extract and summarize relevant findings from inductive analysis. Main results: We identified 23 studies of pregnant people’s views about cannabis use in pregnancy. Comparative analysis revealed that whether cannabis was studied alone or grouped with other substances resulted in significant diversity in descriptions of participant decision-making priorities and perceptions of risks and benefits. Studies combining cannabis with other substance seldom addressed perceived benefits or reasons for using cannabis. Conclusions: The way cannabis is grouped with other substances influences the design and results of research. A comparative analysis emphasizes the importance of understanding why a pregnant person might choose to use cannabis in order to foster dialogue about perceptions of benefit and strategies for risk mitigation.
... Due to their high affinity for the CB1 receptor (Huffman et al., 2005), SCs usually are more potent than natural cannabinoids, with potential health risks. The pattern of acute clinical toxicity associated with the recreational use of SCs is frequently characterized by tachycardia, agitation, and nausea, which typically resolve with symptomatic care (Cohen et al., 2019;Tournebize et al., 2017;Hermanns-Clausen et al., 2013). In some cases, severe toxicity including stroke, seizure, myocardial infarction, rhabdomyolysis, acute kidney injury, psychosis, suicidal ideation, and hyperemesis has been associated with SCs use, and SCs have been directly or indirectly involved in fatal cases (Hermanns-Clausen et al., 2013;Tait et al., 2016). ...
Article
Full-text available
Synthetic cannabinoids (SCs) are a group of new psychoactive drugs used recreationally with potential health risks. They are monitored by the EU Early Warning System since 2010 due to severe adverse effects on consumers. JWH-122 and JWH-210 are naphthoylindole SCs and potent cannabinoid receptor CB1 and CB2 agonists. Information about the effects of SCs usually is available from intoxication cases and surveys, and few studies on humans after controlled administration or observational/naturalistic studies using standardized measures of cardiovascular and subjective effects are available. The aim of this study was to evaluate the acute pharmacological effects of JWH-122 and JWH-210 recreational consumption in a 4 h observational study and assess their disposition in oral fluid (OF). Sixteen volunteers self-administered 1 mg dose of JWH-122 (n = 8) or 2.25 mg mean dose of JWH-210 (range 2–3 mg, n = 8) by inhalation (smoking). Physiological parameters including blood pressure (systolic and diastolic), heart rate (HR), and cutaneous temperature were measured. A set of visual analog scales, the 49-item short-form version of the Addiction Research Center Inventory (ARCI), and the Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) were used for the evaluation of subjective effects. OF was collected at baseline and at 10, 20, and 40 min and 1, 2, 3, and 4 h after self-administration. Statistically significant increases in systolic blood pressure (SBP), diastolic blood pressure (DBP), and HR were observed after JWH-122 self-administration but not after JWH-210 self-administration. JWH-210 self-administration produced significant changes in subjective drug effects, similar to those induced by THC (intensity, high, good effects, and hunger). The subjective effects following JWH-122 consumption were minimal. The maximal effects were mostly observed 20 min after intake. JWH-122 and JWH 210 OF concentration reached a peak 20 min after administration and could not be detected after 3 h. The results demonstrated a different pattern of effects of these two SCs. Due to the limitations of our observational study, further research with a larger sample and controlled studies are needed to better define the acute pharmacological effect and health risk profile of JWH-122 and JWH-210.
... C. sativa plant with the major psychoactive constituent of ∆-9 tetrahydrocannabinol (THC) is the most widely cultivated, trafficked and consumed substance among approximately 147 million people annually, consisting 2.5% of the world population 21 . Although cannabis is used for therapeutic purposes and has wide-ranging potential uses in medicine, with increasing legalization, still the adverse events in central nervous system and other health outcomes limit its adoption. ...
Preprint
ORIGINAL The effect of Cannabis sativa on memory, apoptotic genes and inflammatory cytokines in rat El efecto del Cannabis sativa sobre la memoria, los genes apoptóticos y las citoquinas inflamatorias en la rata Abstract Objectives: Cannabis sativa L. has important ingredients of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). CBD is non-psychotropic, but THC is psychotropic responsible for making people feel "high". This study investigated changes in memory, apoptosis and inflammatory cytokines following C. sativa use in experimental rats. Methods: Forty-five Wistar rats were randomly divided to 3 equal groups of experimental receiving cannabis subcutaneously (2 mg/ kg in 0.6 mL volume) for 3 weeks, sham receiving ethanol identically (0.6 mL), and control receiving normal saline similarly (0.6 mL). The animals' spatial memory was assessed for 3 weeks using mean percentage of alternation and number of entries in a Y-maze to confirm cannabis effect on the brain. Real-time PCR was conducted for expression analysis of primer pairs for Bax and Bcl-2 genes in response to cannabis. Changes in inflammatory cytokines of IL-1, IL-6, IL-10, TNFα, INFγ, superoxidase dismutase (SOD) and malondialdehyde (MDA) were assessed following cannabis use. Results: Significant reduction in memory and expression of Bcl-2 genes and increase in expression of Bax and inflammatory cytokines of IL-1, IL-6, IL-10, TNFα, INFγ and SOD were noted following cannabis use. Conclusions: Based on our findings and reduction in memory and expression of Bcl-2 gene, and increase in expression of Bax gene and inflammatory cytokines following cannabis use, the paramount public health importance of cannabis use, when targeted for medical purposes should come into consideration. Resumen Objetivos: El Cannabis sativa L. tiene importantes ingredientes de delta-9-tetrahidrocannabinol (THC) y cannabidiol (CBD). El CBD no es psicotrópico, pero el THC es psicotrópico, responsable de hacer que las personas se sientan "colocadas". Este estudio investigó los cambios en la memoria, la apoptosis y las citoquinas inflamatorias tras el uso de C. sativa en ratas experimentales. Métodos: Cuarenta y cinco ratas Wistar fueron divididas aleatoriamente en 3 grupos iguales de experimentación que recibieron cannabis por vía subcutánea (2 mg/kg en 0,6 mL de volumen) durante 3 semanas, de simulación que recibieron etanol de forma idéntica (0,6 mL) y de control que recibieron solución salina normal de forma similar (0,6 mL). Se evaluó la memoria espacial de los animales durante 3 semanas utilizando el porcentaje medio de alternancia y el número de entradas en un laberinto en Y para confirmar el efecto del cannabis en el cerebro. Se realizó una PCR en tiempo real para el análisis de la expresión de los pares de cebadores para los genes Bax y Bcl-2 en respuesta al cannabis. Se evaluaron los cambios en las citoquinas inflamatorias de IL-1, IL-6, IL-10, TNFα, INFγ, superoxidasa dismutasa (SOD) y malondialdehído (MDA) tras el consumo de cannabis. Resultados: Se observó una reducción significativa de la memoria y la expresión de los genes Bcl-2 y un aumento de la expresión de Bax y de las citoquinas inflamatorias de IL-1, IL-6, IL-10, TNFα, INFγ y SOD tras el consumo de cannabis. Conclusiones: Basándonos en nuestros hallazgos y en la reducción de la memoria y la expresión del gen Bcl-2, y el aumento de la expresión del gen Bax y de las citoquinas inflamatorias tras el consumo de cannabis, debe tenerse en cuenta la importancia primordial del consumo de cannabis para la salud pública, cuando se destina a fines médicos. Palabras clave: Cannabis sativa, Memoria, Apoptosis, Inflamación. ID ID ID ID 97 2021/36 (4): 96-101 The effect of cannabis sativa on memory, apoptotic genes and inflammatory cytokines in rat
... Adverse event reporting was limited, but most patients seem to tolerate cannabis products. While not noted in included studies, there is a suggestion that cannabis can cause drowsiness, dizziness, or a mental slowing which is something patients should consider [25]. ...
Article
The goal of this systematic review was to define a consensus within the current literature regarding the impact/effect of cannabis or cannabinoids on the treatment of patients with head and neck cancer. We conducted a review of PubMed, Embase, and Web of Science databases, using a comprehensive search strategy, focusing on articles relating to head & neck cancer and cannabis/cannabinoids without a time limit for publication. Two, independent reviewers screened articles based on title/abstract and included the ones selected by both. We then conducted a full-text review and excluded all articles which did not meet inclusion criteria. A single reviewer then assessed studies for methodological quality and extracted relevant data using a premade data collection tool. We identified five studies that met inclusion criteria. Studies were of varying quality and the majority investigated recreational cannabis use with only one study reporting dosing across participants. Lack of standardized cannabis exposure presents a wide array of potential confounding variables across the remaining studies. Meta-analysis was not attempted due to variability in reported outcomes. It is impossible to draw any conclusions regarding the benefit or adverse effects of current medical cannabis products in this patient population. The literature regarding the effect of cannabis/cannabinoids on head & neck cancer patients is limited. However, the current lack of evidence does not definitively disprove the efficacy of cannabis. High-quality studies are necessary for physicians to provide advice to patients who are either using or interested in cannabis as an adjunctive treatment.
... Thus, in the case of cannabinoid overdose, there is no fear of respiratory depression [11]. However, THC and CBD affect receptors not only in the nervous system; they can cause tachycardia, hypotension, muscle relaxation, or impaired gastrointestinal motility [51]. The risk of cannabinoid addiction is lower than for tobacco, alcohol, or cocaine. ...
Article
Full-text available
Cancer is the second leading cause of death worldwide, after cardiovascular diseases. Increasing patients’ awareness and providing easier access to public information result in greater interest in alternative anticancer or unproven supportive therapies. Fear of cancer and limited trust in the treating physician are also important reasons leading patients to seek these methods. Trust and good communication are essential to achieving truthful collaboration between physicians and patients. Given the popularity of CAM, better knowledge about these alternative practices may help oncologists discuss this issue with their patients. This article objectively reviews the most common unconventional therapies used by cancer patients.
... As a result, CBD's safety is simply assumed given it is widely available and lacks the euphoric, psychoactive characteristics of THC [5]. Although the causal relation between cannabis use and its side-effects is not clear now, frequent use of cannabis-based products is associated with some short-and long-term effects like respiratory and cardiovascular disorders, cognitive alterations, psychosis, schizophrenia, and mood disorders [6]. However, Stith et al.'s [7] study shows that CBD, in particular, did not necessarily improve any health issues but neither caused side effects based on self-reporting. ...
Conference Paper
Full-text available
Although the U.S. FDA has only approved exactly one cannabidiol (CBD) drug product (specifically to treat seizures), CBD products are proliferating rapidly through different modes of usage including food products, cosmetics, vaping pods, and supplements (typically, oils). Despite the FDA clearly warning consumers about unproven health claims made by manufacturers selling CBD products over the counter, the CBD market share was nearly 3 billion USD in 2020 and is expected to top 55 billion USD in 2028. In this context, it is important to assess the presence of health claims being made on social media, especially claims that are part of marketing messages. To this end, we collected over two million English tweets discussing CBD themes. We created a hand-labeled dataset and built machine learned classifiers to identify marketing tweets from regular tweets that may be generated by consumers. The best classifier achieved 85% precision, 83% recall, and 84% F-score. Our analyses showed that pain, anxiety disorders, sleep disorders, and stress are the four main therapeutic claims made constituting 31.67%, 27.11%, 13.77%, and 10.37% of all medical claims made on Twitter, respectively. Also, more than 93% of advertised CBD products are edibles or oil/tinctures. Our effort is the first to demonstrate the feasibility of surveillance of marketing claims for CBD products. We believe this could pave way for more explorations into this indispensable task in the current landscape of social media driven health (mis)information and communication.
... Furthermore, as Cohen et al. highlight, cannabis is widely known to cause many psychotropic effects such as euphoria, time distortion, and sensory alterations. Other potential adverse effects of marijuana use include impaired cognitive function, cannabis dependence, and an increased risk of developing psychotic disorders [18]. In that sense, while medical cannabis may help decrease opiate use, the potential of harm due to the adverse effects must be carefully considered. ...
Article
Background Opioid medications are commonly used to treat chronic pain around the world. While these medications are quite effective at reducing pain, they can create opioid dependence and lead to further drug addiction. Long-term opioid use has significantly contributed to the "opioid epidemic" that is currently ravaging the United States, leading to opioid overdoses and unintentional deaths, particularly in Delaware. Objective To determine if medical marijuana certification helps patients in Delaware with chronic pain reduce their opiate use. Methods In this study, we examined individuals who were provided with legal; medical cannabis certifications in the state of Delaware between June 2018 and October 2019 and were concurrently being treated with opioid medications for chronic pain at a private pain management practice. Using a posthoc analysis, we conducted a retrospective cohort study on the individuals (n = 81) to determine if there was a decrease in their opioid use following medical cannabis certification. Opioid use was measured in morphine milligram equivalent (MME) through the Delaware prescription monitoring program (PMP) database. Results Overall, the average change in prescribed opioid use was found to be -12.3 morphine milligram equivalent (MME) units when including all individuals (p < 0.00001). Among the included individuals with baseline opioid use, medical cannabis certification was associated with a 31.3% average decrease in opioid use (n = 63). When examining subgroups based upon pain location, individuals with neck pain displayed a 41.5% average decrease in MME (n = 27), while individuals with low back pain were observed to have a 29.4% decrease in opioid use (n = 58). Similarly, individuals with knee pain (n = 14) reduced their opioid use by 32.6%. Conclusion The results display an association between medical cannabis certification and a decrease in opiate use among the study group individuals. This study suggests that medical cannabis use may help individuals to reduce their opiate requirements along with physician intervention. More research is needed to validate these findings with appropriate controls and verification of cannabis use.
... A 1972 study gave up to 9000 mg/kg of THC to dogs and monkeys without any lethal effects. 35 There have been increasing case reports of cardiovascular deaths with high THC inhaled recreational cannabis use and the newer synthetic THC substitutes 36 and care and careful monitoring should be undertaken in prescribing CBMP for those at risk of cardiovascular disease. 37 However, the long-term effects of regular low-dose CBMP are not available and will require ongoing pharmacovigilance. ...
Article
Cannabis has been used as a medicine for millennia. Prohibition in the mid-20th century precluded early scientific investigation. ‘Cannabis’ describes three separate forms – herbal cannabis, ‘hemp’ products, pharmaceutical-grade regulated cannabinoid-based medical products (CBMP). In Australia, CBMP became available for prescription in November 2016. Herbal cannabis with Δ9-tetrahydrocannabinol (THC), which is illegal, and cannabidiol (CBD) in herbal extracts, are both unregulated and unreliable sources of cannabinoids. The endocannabinoid system (ECS), delineated in the late 1990s, has increased the understanding and interest in research for appropriate clinical indications. The ubiquitous ECS has homeostatic and anti-inflammatory effects and comprises cannabinoid receptors, endocannabinoids and degrading enzymes. Phytocannabinoids are partial agonists of the ECS. In pre-clinical studies, THC and CBD produce beneficial effects in chronic pain, anxiety, sleep and inflammation. Systematic reviews often conflate herbal cannabis and CBMP, confusing the evidence. Currently large randomised controlled trials are unlikely to be achieved. Other methodologies with quality end-points are required. Rich, valuable high-quality real-world evidence for the safe and effective use of CBMP provides an opportunity to examine benefits and potential harms. Evidence demonstrates benefit of CBMP in multiple sclerosis, chronic neuropathic pain, chemotherapy induced nausea and vomiting, resistant paediatric epilepsy, anxiety and insomnia. CBMP are well tolerated with few serious adverse events. Additional clinical benefits are promising in many other resistant chronic conditions. Pharmaceutical grade prescribed CBMP has proven clinical benefits and provides another clinical option in the physician's pharmacopeia.
... The effectiveness and safety are the primary objectives for hunting a new drug as all drugs can help to combat diseases as well as cause harmful effects [50]. In silico analysis has played an increasingly significant part in the drug research and discovery by providing an effective way to assess multiple pharmacokinetics properties [51]. ...
Article
Full-text available
Diabetes mellitus termed as metabolic disorder is a collection of interlinked diseases and mainly body's inability to manage glucose level which leads to cardiovascular diseases, renal failure, neurological disorders, and many others. The drugs contemporarily used for diabetes have many inevitable side effects, and many of them have become less responsive to this multifactorial disorder. Momordica charantia commonly known as bitter gourd has many bioactive compounds with antidiabetic properties. The current study was designed to use computational methods to discover the best antidiabetic peptides devised from hypoglycemic polypeptide-P of M. charantia. The binding affinity and interaction patterns of peptides were evaluated against four receptor proteins (i.e., as agonists of insulin receptor and inhibitors of sodium-glucose cotransporter 1, dipeptidyl peptidase-IV, and glucose transporter 2) using molecular docking approach. A total of thirty-seven peptides were docked against these receptors. Out of which, top five peptides against each receptor were shortlisted based on their S-scores and binding affinities. Finally, the eight best ligands (i.e., LIVA, TSEP, EKAI, LKHA, EALF, VAEK, DFGAS, and EPGGGG) were selected as these ligands strictly followed Lipinski's rule of five and exhibited good ADMET profiling. One peptide EPGGGG showed activity towards insulin and SGLT1 receptor proteins. The top complex for both these targets was subjected to 50 ns of molecular dynamics simulations and MM-GBSA binding energy test that concluded both complexes as highly stable, and the intermolecular interactions were dominated by van der Waals and electrostatic energies. Overall, the selected ligands strongly fulfilled the drug-like evaluation criterion and proved to have good antidiabetic properties.
Article
Owing to its psychotropic effects, Cannabis has been stigmatized by its recreational use leading to a dramatic decline in the experimentations about its medical use in the twentieth century. The medical properties of the plant – known since ancient times – has received increased attention over recent years; yet, the research on its potential application in the field of psychiatry is still nascent. In this connection, the non-psychotropic cannabidiol (CBD) has emerged as a phytocannabinoid compound with promising antipsychotic effects. In addition, advances in our understanding of the endocannabinoid system, along with accumulating evidence implicating this system in the pathophysiology of schizophrenia, have stimulated research by the pharmaceutical industry to explore whether alteration of this system can be of medical benefit. This review examines the current state of evidence regarding the clinical potential of cannabinoid-based drugs as a treatment for schizophrenia, while discussing various limitations with the therapeutic approaches considered so far. In the second part, the author highlights the most promising strategies, as well as the most interesting directions one could follow, in the emerging field of cannabinoid therapies for schizophrenia.
Article
Introduction Neuropathic pain is a debilitating condition caused by lesion or disease of the somatosensory nervous system. Integrative modalities such as yoga, acupuncture, and massage are evidenced therapies for pain management. Additionally, medical cannabis and cannabinoids are emerging therapies for treatment of neuropathic pain (4,28). The authors of this study report a case of chronic neuropathic pain treated with integrative interventions. Case Presentation The patient is a 71-year-old female with a past medical history of chronic neuropathic pain in her lower back and legs, degenerative arthritis, restless leg syndrome, carpal tunnel syndrome, and severe, chronic anxiety, presenting with worsening neuropathic pain. After over a decade of unsuccessful allopathic treatment, the patient sought out a more integrative approach to her pain management. A regimen of acupuncture, massage, gentle yoga, and medical cannabis was recommended. During the COVID-19 pandemic, she was unable to continue most of the integrative modalities and reported a significant increase in pain. The patient then joined a weekly Mind and Body program and began acupuncture treatments again, reporting a steady improvement in pain. Conclusion The patient's chronic neuropathic pain was effectively treated using an integrative approach, with a combination of acupuncture, massage, yoga, mind-body approaches, and medical cannabis. While this case originally presented similarly to other cases of chronic neuropathic pain, it is unique in that it demonstrates the importance of an individualized complex approach, highlighting the patient's driven engagement in integrative modalities and medical cannabis.
Article
Full-text available
Background Poisoning is one of the leading causes of admission to the emergency department and intensive care unit. A large number of epidemiological changes have occurred over the last years such as the exponential growth of new synthetic psychoactive substances. Major progress has also been made in analytical screening and assays, enabling the clinicians to rapidly obtain a definite diagnosis. Methods A committee composed of 30 experts from five scientific societies, the Société de Réanimation de Langue Française (SRLF), the Société Française de Médecine d’Urgence (SFMU), the Société de Toxicologie Clinique (STC), the Société Française de Toxicologie Analytique (SFTA) and the Groupe Francophone de Réanimation et d’Urgences Pédiatriques (GFRUP) evaluated eight fields: (1) severity assessment and initial triage; (2) diagnostic approach and role of toxicological analyses; (3) supportive care; (4) decontamination; (5) elimination enhancement; (6) place of antidotes; (7) specificities related to recreational drug poisoning; and (8) characteristics of cardiotoxicant poisoning. Population, Intervention, Comparison, and Outcome (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Analysis of the literature and formulation of recommendations were then conducted according to the GRADE ® methodology. Results The SRLF-SFMU guideline panel provided 41 statements concerning the management of pharmaceutical and recreational drug poisoning. Ethanol and chemical poisoning were excluded from the scope of these recommendations. After two rounds of discussion and various amendments, a strong consensus was reached for all recommendations. Six of these recommendations had a high level of evidence (GRADE 1±) and six had a low level of evidence (GRADE 2±). Twenty-nine recommendations were in the form of expert opinion recommendations due to the low evidences in the literature. Conclusions The experts reached a substantial consensus for several strong recommendations for optimal management of pharmaceutical and recreational drug poisoning, mainly regarding the conditions and effectiveness of naloxone and N -acetylcystein as antidotes to treat opioid and acetaminophen poisoning, respectively.
Article
Although several extraction methodologies have been reported to date, the development of novel, more powerful, and alternative extraction processes using hemp as the vegetable matrix is still a challenging field of research. In this manuscript the performance of the subcritical butane promoted extraction of a panel of 5 non psychoactive cannabinoids from hemp inflorescences from 2 hemp varieties, under a counter-current mode using a handmade extraction apparatus,was studied. All secondary metabolites under investigation have been finally quantified by gas chromatographic analyses coupled to mass spectrometry. Phyto canabinoids have been extracted in yields from 3.3-fold to 55-fold higher with respect to traditional methods that were adopted herein as a comparison. The use of subcritical butane as the extraction solvent for cannabinoids from hemp inflorescences is reported herein for the first time and could be easily adopted for other matrices (e.g. seeds) deriving from the same vegetable source.
Article
Hepatocellular carcinoma (HCC) is the most common type of liver cancer worldwide. Viral hepatitis is a significant risk factor for HCC, although metabolic syndrome and diabetes are more frequently associated with the HCC. With increasing prevalence, there is expected to be > 1 million cases annually by 2025. Therefore, there is an urgent need to establish potential therapeutic targets to cure this disease. Peroxisome-proliferator-activated receptor gamma (PPARγ) is a ligand-activated transcription factor that plays a crucial role in the pathophysiology of HCC. Many synthetic agonists of PPARγ suppress HCC in experimental studies and clinical trials. These synthetic agonists have shown promising results by inducing cell cycle arrest and apoptosis in HCC cells and preventing the invasion and metastasis of HCC. However, some synthetic agonists also pose severe side effects in addition to their therapeutic efficacy. Thus natural PPARγ agonists can be an alternative to exploit this potential target for HCC treatment. In this review, the regulatory role of PPARγ in the pathogenesis of HCC is elucidated. Furthermore, the experimental and clinical scenario of both synthetic and natural PPARγ agonists against HCC is discussed. Most of the available literature advocates PPARγ as a potential therapeutic target for the treatment of HCC.
Article
Few studies have compared knowledge of the specific health risks of cannabis across jurisdictions. This study aimed to examine perceptions of the health risks of cannabis in Canada and US states with and without legal non-medical cannabis. Cross-sectional data were collected from the 2018 and 2019 International Cannabis Policy Study online surveys. Respondents aged 16-65 (n = 72 459) were recruited from Nielsen panels using non-probability methods. Respondents completed questions on nine health effects of cannabis (including two 'false' control items). Socio-demographic data were collected. Regression models tested differences in outcomes between jurisdictions and by frequency of cannabis use, adjusting for socio-demographic factors. Across jurisdictions, agreement with statements on the health risks of cannabis was highest for questions on driving after cannabis use (66-80%), use during pregnancy/breastfeeding (61-71%) and addiction (51-62%) and lowest for risk of psychosis and schizophrenia (23-37%). Additionally, 12-18% and 6-7% of respondents agreed with the 'false' assertions that cannabis could cure/prevent cancer and cause diabetes, respectively. Health knowledge was highest among Canadian respondents, followed by US states that had legalized non-medical cannabis and lowest in states that had not legalized non-medical cannabis (P < 0.001). Overall, the findings demonstrate a substantial deficit in knowledge of the health risks of cannabis, particularly among frequent consumers.
Article
Full-text available
Introdução. Os produtos comestíveis à base de maconha tornaram-se um mercado lucrativo e de grande procura. Apesar de no Brasil não ser legalizada, a maconha é encontrada em preparações orais comercializadas ilegalmente no país e a busca por esses produtos tem crescido nos últimos anos. O presente estudo tem por finalidade reunir dados da literatura científica sobre a fisiologia do sistema endocanabinóide, efeitos do consumo de Cânabis por via oral, farmacocinética, possíveis efeitos tóxicos, terapêuticos e formas de detecção, buscando contribuir para o preenchimento da lacuna ainda existente sobre o tema. Metodologia. Foi realizada revisão integrativa na base de dados PubMed para publicações dos últimos 5 anos em português, inglês e espanhol. Resultados. A pesquisa resultou em 128 artigos os quais foram removidos os trabalhos que não preenchessem os critérios de inclusão, restando 28 artigos utilizados. Conclusões. É necessário que seja realizado um número maior de ensaios clínicos com canabis por via oral, nas diversas formulações existentes, para melhor compreender sua farmacocinética, farmacodinâmica, potencialidades terapêuticas e seus efeitos adversos.
Article
Full-text available
This is the pre-peer reviewed version of the following article: Sorensen, J. L., van Draanen, J., & Shingle, M. Legalization of cannabis in Canada—Local media analysis. The American Journal on Addictions., which has been published in final form at 10.1111/ajad.13263. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. Background and objectives: Legalization of recreational cannabis is occurring across the United States, with some controversy. To understand the range of issues that can arise when such a policy change is enacted, we examined portrayal of legalization at the local level by studying newspaper articles in Calgary, Alberta, shortly before and after cannabis legalization in Canada. Method: We searched the largest-circulation newspaper for cannabis-related items and analyzed for content and slant toward cannabis legalization. Results: Among 165 items, business/economics (70.9% of items) and legalization (69.7%) were most frequent, with health only 29.7%. Across all items, the slant was more approval (44.2%) than disapproval (23.0%). Discussion and conclusions: When cannabis was legalized, the local newspaper focused more on economic aspects of legalization rather than about health issues. Further research can determine the generalizability of the findings to other locales and provide comparison as other similar policy changes roll out. Scientific significance: The study provides new information on what happens when drug policies are enacted. Documenting the media portrayal of substance use policies is a promising tool.
Article
Full-text available
Article
Introduction As cannabis use rises among adults in the U.S., driving under the influence of cannabis represents a public health concern. Methods In 2020, public-use data from the National Survey on Drug Use and Health were examined, using an analytic sample of 128,205 adults interviewed between 2016 and 2018. The annual prevalence of driving under the influence of cannabis was computed overall, by state, by demographic group, and among cannabis users. Demographic, psychosocial, and behavioral correlates of driving under the influence were tested by multivariate logistic regression. Results The self-reported annual prevalence of driving under the influence of cannabis was 4.5% (95% CI=4.3, 4.6) among U.S. adults, ranging from 3.0% (Texas) to 8.4% (Oregon) in individual U.S. states. Among cannabis users, 29.5% (95% CI=28.6, 30.3) reported driving under the influence of cannabis; the predicted probabilities of driving under the influence of cannabis were highest for those with more frequent use, with daily cannabis users evidencing a 57% predicted probability. Among individuals with symptoms suggestive of a cannabis use disorder, the prevalence of driving under the influence of cannabis was 63.8% (95% CI=60.8, 66.6). Among cannabis users, those reporting driving under the influence of cannabis had higher odds of driving under the influence of other illicit substances, using other illicit drugs, taking part in illegal behavior, and suffering from mental distress, after adjusting for demographic characteristics and psychosocial/behavioral correlates. Conclusions Findings suggest that prevention efforts should focus on frequent and problem cannabis users and should include content related to other illicit drug use and other drug-impaired driving.
Article
Full-text available
Zinc has so many beneficial effects as a supplement, particularly for the treatment of diseases and prevention of the occurrence of several disorders through inflammatory reactions, especially in gastrointestinal cases. The present study was done to assess the Zn effect on Silent Information Regulator 1 (SIRT1) and Peroxisome proliferator activated receptor γ coactivator-1α (PGC-1α) gene expression among ulcerative colitis (UC) patients. Fifty patients with mild-to-moderate active UC were included and divided into two groups of treatment (25 patients received Zn (35 mg Zn gluconate/day for 40 days) and control (25 patients received placebo similar to the Zn capsules in shape and color for 40 days). The expression rates of SIRT1 and PGC-1α were examined in the patients using the Real-Time PCR. The mean age of included patients was 37.2±10.6 years. The male to female ratio was 23/27. Totally, the distribution of smoking and alcohol among patients were 55% and 31%, respectively. Pan UC (40%) and lift-sided (40%) had the higher distribution. The mean expression of the PGC1-α gene was increased amongst the UC patients treated with Zn supplement (P <0.05). The mean expression of the SIRT1 gene was increased amongst the UC patients treated with Zn supplement (P <0.05). However, in the control group, no any changes have been recorded for both genes. It seems that Zn caused significant decrease in the inflammatory response of the colon by significant increase in the expression of the SIRT1 and PGC1-α genes. Keywords: Ulcerative colitis, PGC1-α, SIRT1, Gene expression, Zinc supplement.
Article
Purpose This study estimated self-reported perceived negative marijuana use consequences among a national sample of U.S. young adults, examining consequence prevalence differences by use frequency, college attendance, living situation, employment, sex, and race/ethnicity; and use frequency/sociodemographic characteristic interactions. Methods A subsample of 1,212 respondents from the 2004–2018 class cohorts of 12th grade students participating in the nationally-representative Monitoring the Future study was surveyed up to two times from modal ages 19 through 22 (in 2008–2019). Respondents self-reported negative consequences related to their own past 12-month marijuana use. Bivariate and multivariable models examined subgroup differences in consequence prevalence. Results Approximately 60% of those using frequently (20+ use occasions in the past 30 days) and 35% of those using non-frequently reported negative consequences. Among all young adult marijuana users, 31.1% reported emotional/physical consequences, 12.9% performance/financial consequences, and 12.3% relational consequences. Use frequency was positively associated with consequence likelihood, excluding regret and unsafe driving. Among college students, frequent use was more strongly associated with any and performance/financial consequences. Controlling for use frequency, men reported more performance/financial consequences; relational consequences were higher among Hispanic (vs. White) respondents, and those living with parents, employed full-time, and not attending 4-year colleges. Conclusion Young adults using marijuana reported a wide range of negative use consequences; likelihood of most consequences increased with higher use frequency. Perceived consequences varied by college attendance, living situation, employment, sex, and race/ethnicity. Efforts to reduce negative marijuana consequences may be strengthened by recognizing and addressing the different types of negative consequences users perceive.
Article
Abstarct Background Given changes in marijuana regulations, retail, and products and potential impact on use, we examined young-adult perceptions of different modes of use, the proportion using via different modes (e.g. smoking, vaping, ingesting), and associations with the use levels and stability of use over time. Methods We analyzed baseline and one-year follow-up survey data (Fall 2018–2019) among 3,006 young adults (ages 18–34) across six metropolitan areas (Atlanta, Boston, Minneapolis-St. Paul, Oklahoma City, San Diego, Seattle). Measures included marijuana use frequency and mode, sociodemographics, other substance use, and social influences. Results Participants’ rated the following modes of use as: least harmful/addictive: topicals, oral pills, joint/bowl; most socially acceptable: joint/bowl, edibles/beverages, vaporized; and most harmful/addictive and least acceptable: wrapped, vaped, or waterpipe/bong with tobacco. Baseline past-month use prevalence was 39.2% (n = 1,178). Most frequent use mode was smoking (joints/bowls/cigar papers; 54.0%), vaping (21.8%), via pipe/bong (15.1%), and ingesting (9.1%). Multinomial logistic regression indicated that participants in states with legalized marijuana retail were at greater odds for using via modes other than smoking; participants more frequently using were at greater odds for using via pipe/bong (vs. smoking) (ps < .001). Regarding most frequent mode across time, most consistent was pipe/bong (53.3%), followed by smoking (49.3%), vaping (44.5%), and ingesting (32.9%). Past-month abstinence at follow-up was most common among those originally ingesting (34.3% abstinent), followed by smoking (23.6%), vaping (18.8%), and pipe/bong (14.8%). Conclusions Ongoing surveillance is needed to understand marijuana use patterns over time across different user groups (particularly by mode) and to inform interventions promoting abstinence.
Article
Background While research has assessed correlates of marijuana use, there has been less focus on predictors of differing levels of changes in use during young adulthood, a critical period for use/escalation. Objectives We examined changes in marijuana use and related sociocontextual predictors (e.g., earlier-onset substance use, parental use, college type). Methods Using data from Georgia college students (ages 18–25 years) in a 2-year, 6-wave longitudinal study (64.6% female, 63.4% White), 2-part random-effects modeling examined use at any assessment and number of days used. Results Predictors of use status at any assessment included being male (OR = 1.87, 95%CI = [1.28–2.73]), Black (OR = 1.91, 95%CI = [1.15–3.19]), earlier-onset marijuana (OR = 2.63, 95%CI = [1.70–4.06]), cigarette (OR = 2.04, 95%CI = [1.19–3.48]), and alcohol users (OR = 1.49, 95%CI = 1.00–2.22]), parental tobacco (OR = 2.14, 95%CI = [1.18–3.86]) and/or alcohol use (OR = 1.55, 95%CI = [1.09–2.20]), and attending private (vs. public) institutions (OR = 1.68, 95%CI = [1.10–2.59]). Predictors of lower likelihood of use over time included being male (OR = 0.87, 95%CI = [0.77–0.98]), earlier-onset cigarette use (OR = 0.82, 95%CI = [0.68–0.98]), parental alcohol use (OR = 0.86, 95%CI = [0.77–0.97]), and private institution students (OR = 1.17, 95%CI = [1.02–1.34]). Predictors of more days used at baseline included being male (OR = 1.77, 95%CI = [1.40–2.23]), Black (OR = 1.42, 95%CI = [1.04–1.93]), earlier-onset marijuana (OR = 2.32, 95%CI = [1.78–3.01]) and alcohol users (OR = 1.29, 95%CI = [1.01–1.66]), and parental tobacco use (OR = 1.90, 95%CI = [1.32–2.73]). Predictors of fewer days used over time included being older (OR = 0.98, 95%CI = [0.97–1.00]), parental tobacco use (OR = 0.86, 95%CI = [0.78–0.95]), and attending private institutions (OR = 0.89, 95%CI = [0.83–0.93]). Conclusions Intervention efforts can be informed by current findings that correlates of baseline use (e.g., being male, attending private institutions) also predicted less use over time, and one’s earlier use and parents’ use of various substances impacted young adult use.
Article
Background: Cannabis plant extracts suppress gastric acid secretion and inflammation, and promote gastroduodenal ulcer healing, all of which are triggered by Helicobacter Pylori infection (HPI). Here, we evaluate the association between cannabis use and HPI among a representative community sample. Materials and Methods: We identified respondents who completed cannabis use questions and were tested for HPI (H. pylori IgG antibody seropositivity) from the National Health and Nutrition Examination Survey III dataset (n=4556). Cannabis usage was categorized as ever-use (ever, never), cumulative lifetime use (>10-times, 1-10-times, never), or recent use (>31-days-ago, within-31-days, never). We calculated the crude and adjusted risk (prevalence rate ratio, cPRR and aPRR) of having HPI with cannabis use using generalized Poisson models (SAS 9.4). The models were adjusted for demographics and risk factors for HPI. Results: The prevalence of HPI was lower among ever versus never cannabis users (18.6% vs. 33%, p<0.0001). Cannabis use was associated with a decreased risk of HPI (cPRR: 0.56 confidence interval [95% CI: 0.47-0.67]; p<0.0001), which persisted after adjusting for demographics (aPRR: 0.75 [95% CI: 0.63-0.90]; p=0.0016) and comorbidities (aPRR: 0.79 [95% CI: 0.66-0.95]; p=0.0145). Further, individuals with >10-times lifetime cannabis use had a decreased risk of HPI compared with those with 1-10-times lifetime use (aPRR: 0.70 [95% CI: 0.55-0.89]; p=0.0011) and never-users (aPRR: 0.65 [95% CI: 0.50-0.84]; p=0.0002). Conclusion: Recreational cannabis use is associated with diminished risk of HPI. These observations suggest the need for additional research assessing the effects of medical cannabis formulations on HPI.
Article
Full-text available
Background: Cannabis is a psychedelic substance that is being abused by millions of people the world. The aim of this study was to investigate the effect of cannabis on the growth of mesenchymal stem cells (msc) derived from endometrium in adult rats. Materials and Methods: In this experimental study, msc were extracted from the endometrium of rats and after culturing and confirming the mesenchymal nature of the cells by flowcytometry and by expressingCD34 and CD90 and not expressingCD105 markers, in the third passage of cell culture, the effects of cannabis in concentration of100 and1000ng/ml were calculated on the growth of these cells within 1to8days by the PDT=T×ln2/ln⁡〖Xe/Xb〗 formula and the results were analyzed using ANOVA and Tuki tests. Results: Cells isolated from the endometrium adhered to the floor of the cell culture flask 24hours after transfer. The mesenchymal nature of these cells was confirmed by the expression of CD90, CD105 and non-expression of CD34markers.The results of cell counts also showed the growth of cells treated with cannabis until the third day of treatment similar to the control group. From the fourth day in the treatment group with a dose of100ng/ml cannabis increased significantly.
Chapter
Cannabinoids were initially found in the cannabis plant; however, they now refer to all those substances capable of activating cannabinoid receptors. Cannabinoids exert both toxic and therapeutic effects through the endocannabinoid system. The existing preclinical and clinical evidence are proposing a possible role for this system in the pathophysiology of depression, though its function in this mental disease has not been fully elucidated yet. It has been proved that a disruption in the endocannabinoid signaling leads to a “depressive-like” phenotype in animal models, which is incongruent with clinical findings where the level of endocannabinoids has declined in depressed patients. Consequently, the facilitation of the endocannabinoid tone induces antidepressant responses. Following the introduction of the endocannabinoid system, this chapter summarizes the basic and clinical evidence indicating the role of endocannabinoids in depressive disorder and then discusses the possible mechanisms of their effects that may function as a key player in the pathogenesis of the depression.
Article
Full-text available
As part of an increasing worldwide use of designer drugs, recent use of compounds containing cathinones and synthetic cannabinoids is especially prevalent. Here, we reviewed current literature on the prevalence, epidemiology, bio-behavioral effects, and detection of these compounds. Gender differences and clinical effects will also be examined. Chronic use of synthetic cathinone compounds can have major effects on the central nervous system and can induce acute psychosis, hypomania, paranoid ideation, and delusions, similar to the effects of other better-known amphetamine-type stimulants. Synthetic cannabinoid products have effects that are somewhat similar to those of natural cannabis but more potent and long-lasting than THC. Some of these compounds are potent and dangerous, having been linked to psychosis, mania, and suicidal ideation. Novel compounds are developed rapidly and new screening techniques are needed to detect them as well as a rigorous regulation and legislation reinforcement to prevent their distribution and use. Given the rapid increase in the use of synthetic cathinones and cannabinoid designer drugs, their potential for dependence and abuse, and harmful medical and psychiatric effects, there is a need for research and education in the areas of prevention and treatment.
Article
Full-text available
Purpose of Review The lack of clarity about the effect of cannabis use on cognition may be attributable to the considerable heterogeneity among studies in terms of cannabis composition. This article selectively reviews studies examining the distinctive effects of cannabinoids on human cognition, particularly those of delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). Recent Findings Research indicates that ∆9-THC administration acutely impairs cognition, particularly memory and emotional processing. Limited evidence suggests that CBD administration might improve cognition in cannabis users but not in individuals with neuropsychiatric disorders. Moreover, studies indicate that some acute Δ9-THC-induced cognitive impairments may be prevented if Δ9-THC is administered in combination or following CBD treatment. Δ9-THC and CBD have also shown opposite effects on cognition-related brain activation, possibly reflecting their antagonistic behavioral effects. Summary Research suggests greater cognitive impairments in individuals when exposed to high ∆9-THC or low CBD cannabis. It is unclear whether at specific concentrations CBD might outweigh any harmful effects of Δ9-THC on cognition.
Article
Full-text available
Importance With rising rates of marijuana use in the general population and an increasing number of states legalizing recreational marijuana use and authorizing medical marijuana programs, there are renewed clinical and policy concerns regarding the mental health effects of cannabis use.Objective To examine prospective associations between cannabis use and risk of mental health and substance use disorders in the general adult population.Design, Setting, and Participants A nationally representative sample of US adults aged 18 years or older was interviewed 3 years apart in the National Epidemiologic Survey on Alcohol and Related Conditions (wave 1, 2001-2002; wave 2, 2004-2005). The primary analyses were limited to 34 653 respondents who were interviewed in both waves. Data analysis was conducted from March 15 to November 30, 2015.Main Outcomes and Measures We used multiple regression and propensity score matching to estimate the strength of independent associations between cannabis use at wave 1 and incident and prevalent psychiatric disorders at wave 2. Psychiatric disorders were measured with a structured interview (Alcohol Use Disorder and Associated Disabilities Interview Schedule–DSM-IV). In both analyses, the same set of wave 1 confounders was used, including sociodemographic characteristics, family history of substance use disorder, disturbed family environment, childhood parental loss, low self-esteem, social deviance, education, recent trauma, past and present psychiatric disorders, and respondent’s history of divorce.Results In the multiple regression analysis of 34 653 respondents (14 564 male [47.9% weighted]; mean [SD] age, 45.1 [17.3] years), cannabis use in wave 1 (2001-2002), which was reported by 1279 respondents, was significantly associated with substance use disorders in wave 2 (2004-2005) (any substance use disorder: odds ratio [OR], 6.2; 95% CI, 4.1-9.4; any alcohol use disorder: OR, 2.7; 95% CI, 1.9-3.8; any cannabis use disorder: OR, 9.5; 95% CI, 6.4-14.1; any other drug use disorder: OR, 2.6; 95% CI, 1.6-4.4; and nicotine dependence: OR, 1.7; 95% CI, 1.2-2.4), but not any mood disorder (OR, 1.1; 95% CI, 0.8-1.4) or anxiety disorder (OR, 0.9; 95% CI, 0.7-1.1). The same general pattern of results was observed in the multiple regression analyses of wave 2 prevalent psychiatric disorders and in the propensity score–matched analysis of incident and prevalent psychiatric disorders.Conclusions and Relevance Within the general population, cannabis use is associated with an increased risk for several substance use disorders. Physicians and policy makers should take these associations of cannabis use under careful consideration.
Article
Full-text available
Context: Synthetic cannabinoids (SCs) such as "Spice", "K2", etc. are widely available via the internet despite increasing legal restrictions. Currently, the prevalence of use is typically low in the general community (<1%) although it is higher among students and some niche groups subject to drug testing. Early evidence suggests that adverse outcomes associated with the use of SCs may be more prevalent and severe than those arising from cannabis consumption. Objectives: To identify systematically the scientific reports of adverse events associated with the consumption of SCs in the medical literature and poison centre data. Method: We searched online databases (Medline, PsycInfo, Embase, Google Scholar and Pubmed) and manually searched reference lists up to December 2014. To be eligible for inclusion, data had to be from hospital, emergency department, drug rehabilitation services or poison centre records of adverse events involving SCs and included both self-reported and/or analytically confirmed consumption. Results: From 256 reports, we identified 106 eligible studies including 37 conference abstracts on about 4000 cases involving at least 26 deaths. Major complications include cardiovascular events (myocardial infarction, ischemic stroke and emboli), acute kidney injury (AKI), generalized tonic-clonic seizures, psychiatric presentations (including first episode psychosis, paranoia, self-harm/suicide ideation) and hyperemesis. However, most presentations were not serious, typically involved young males with tachycardia (≈37-77%), agitation (≈16-41%) and nausea (≈13-94%) requiring only symptomatic care with a length of stay of less than 8 hours. Conclusions: SCs most frequently result in tachycardia, agitation and nausea. These symptoms typically resolve with symptomatic care, including intravenous fluids, benzodiazepines and anti-emetics, and may not require inpatient care. Severe adverse events (stroke, seizure, myocardial infarction, rhabdomyolysis, AKI, psychosis and hyperemesis) and associated deaths manifest less commonly. Precise estimates of their incidence are difficult to calculate due to the lack of widely available, rapid laboratory confirmation, the variety of SC compounds and the unknown number of exposed individuals. Long-term consequences of SCs use are currently unknown.
Article
Full-text available
There is extensive research on the safety, toxicology, potency, and therapeutic potential of cannabis. However, uncertainty remains facilitating continued debate on medical and recreational cannabis policies at the state and federal levels. This review will include a brief description of cannabinoids and the endocannabinoid system; a summary of the acute and long-term effects of cannabis; and a discussion of the therapeutic potential of cannabis. The conclusions about safety and efficacy will then be compared with the current social and political climate to suggest future policy directions and general guidelines. Electronic supplementary material The online version of this article (doi:10.1007/s13311-015-0380-8) contains supplementary material, which is available to authorized users.
Article
Full-text available
Cannabis and cannabinoid drugs are widely used to treat disease or alleviate symptoms, but their efficacy for specific indications is not clear. To conduct a systematic review of the benefits and adverse events (AEs) of cannabinoids. Twenty-eight databases from inception to April 2015. Randomized clinical trials of cannabinoids for the following indications: nausea and vomiting due to chemotherapy, appetite stimulation in HIV/AIDS, chronic pain, spasticity due to multiple sclerosis or paraplegia, depression, anxiety disorder, sleep disorder, psychosis, glaucoma, or Tourette syndrome. Study quality was assessed using the Cochrane risk of bias tool. All review stages were conducted independently by 2 reviewers. Where possible, data were pooled using random-effects meta-analysis. Patient-relevant/disease-specific outcomes, activities of daily living, quality of life, global impression of change, and AEs. A total of 79 trials (6462 participants) were included; 4 were judged at low risk of bias. Most trials showed improvement in symptoms associated with cannabinoids but these associations did not reach statistical significance in all trials. Compared with placebo, cannabinoids were associated with a greater average number of patients showing a complete nausea and vomiting response (47% vs 20%; odds ratio [OR], 3.82 [95% CI, 1.55-9.42]; 3 trials), reduction in pain (37% vs 31%; OR, 1.41 [95% CI, 0.99-2.00]; 8 trials), a greater average reduction in numerical rating scale pain assessment (on a 0-10-point scale; weighted mean difference [WMD], -0.46 [95% CI, -0.80 to -0.11]; 6 trials), and average reduction in the Ashworth spasticity scale (WMD, -0.36 [95% CI, -0.69 to -0.05]; 7 trials). There was an increased risk of short-term AEs with cannabinoids, including serious AEs. Common AEs included dizziness, dry mouth, nausea, fatigue, somnolence, euphoria, vomiting, disorientation, drowsiness, confusion, loss of balance, and hallucination. There was moderate-quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity. There was low-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep disorders, and Tourette syndrome. Cannabinoids were associated with an increased risk of short-term AEs.
Article
Full-text available
A subset of patients with multiple sclerosis (MS) smoke cannabis to relieve symptoms including spasticity and pain. Recent evidence suggests that smoking cannabis further impairs cognition in people with MS and is linked to impaired functional brain changes. No such association, however, has been reported between cannabis use and structural brain changes, hence the focus of the present study. Twenty patients with MS who smoke cannabis for symptom relief, and 19 matched non-cannabis-smoking MS patients were given the Brief Repeatable Neuropsychological Battery and structural MRI scans. Images were segmented into gray matter and white matter, and subsequently analysed with Partial Least Squares, a data-driven multivariate technique that explores brain-behaviour associations. In both groups, the Partial Least Squares analysis yielded significant correlations between cognitive scores and both gray matter (33% variance, p < .0001) and white matter (17% variance, p < .05) volume. Gray matter volume in the thalamus, basal ganglia, medial temporal, and medial prefrontal regions, and white matter volume in the fornix correlated with cognitive deficits. Crucially, the analysis indicated that brain volume reductions were associated with more extensive cognitive impairment in the cannabis versus the non-cannabis MS group. These results suggest that cannabis use in MS results in more widespread cognitive deficits, which correlate with tissue volume in subcortical, medial temporal, and prefrontal regions. These are the first findings demonstrating an association between cannabis use, cognitive impairment and structural brain changes in MS patients.
Article
Full-text available
Background The risk of individuals having adverse eff ects from drug use (eg, alcohol) generally depends on the frequency of use and potency of the drug used. We aimed to investigate how frequent use of skunk-like (high-potency) cannabis in south London aff ected the association between cannabis and psychotic disorders.
Article
Full-text available
Background: The risk of individuals having adverse effects from drug use (eg, alcohol) generally depends on the frequency of use and potency of the drug used. We aimed to investigate how frequent use of skunk-like (high-potency) cannabis in south London affected the association between cannabis and psychotic disorders. Methods: We applied adjusted logistic regression models to data from patients aged 18-65 years presenting to South London and Maudsley NHS Foundation Trust with first-episode psychosis and population controls recruited from the same area of south London (UK) to estimate the effect of the frequency of use, and type of cannabis used on the risk of psychotic disorders. We then calculated the proportion of new cases of psychosis attributable to different types of cannabis use in south London. Findings: Between May 1, 2005, and May 31, 2011, we obtained data from 410 patients with first-episode psychosis and 370 population controls. The risk of individuals having a psychotic disorder showed a roughly three-times increase in users of skunk-like cannabis compared with those who never used cannabis (adjusted odds ratio [OR] 2·92, 95% CI 1·52-3·45, p=0·001). Use of skunk-like cannabis every day conferred the highest risk of psychotic disorders compared with no use of cannabis (adjusted OR 5·4, 95% CI 2·81-11·31, p=0·002). The population attributable fraction of first-episode psychosis for skunk use for our geographical area was 24% (95% CI 17-31), possibly because of the high prevalence of use of high-potency cannabis (218 [53%] of 410 patients) in our study. Interpretation: The ready availability of high potency cannabis in south London might have resulted in a greater proportion of first onset psychosis cases being attributed to cannabis use than in previous studies. Funding: UK National Institute of Health Research (NIHR) Specialist Biomedical Research Centre for Mental Health, SLaM and the Institute of Psychiatry at King's College London, Psychiatry Research Trust, Maudsley Charity Research Fund, and th European Community's Seventh Framework Program grant (agreement No. HEALTH-F2-2009-241909 [Project EU-GEI]).
Article
Full-text available
Cannabis use is associated with an increased risk of psychosis in vulnerable individuals. Cannabis containing high levels of the partial cannabinoid receptor subtype 1 (CB1) agonist tetrahydrocannabinol (THC) is associated with the induction of psychosis in susceptible subjects and with the development of schizophrenia, whereas the use of cannabis variants with relatively high levels of cannabidiol (CBD) is associated with fewer psychotic experiences. Synthetic cannabinoid receptor agonists (SCRAs) are full agonists and often more potent than THC. Moreover, in contrast to natural cannabis, SCRAs preparations contain no CBD so that these drugs may have a higher psychosis-inducing potential than cannabis. This paper reviews the general toxicity profile and the adverse effects of SCRAs with special emphasis on their psychosis-inducing risk. The review shows that, compared with the use of natural cannabis, the use of SCRAs may cause more frequent and more severe unwanted negative effects, especially in younger, inexperienced users. Psychosis and psychosis-like conditions seem to occur relatively often following the use of SCRAs, presumably due to their high potency and the absence of CBD in the preparations. Studies on the relative risk of SCRAs compared with natural cannabis to induce or evoke psychosis are urgently needed. © The Author(s) 2015.
Article
Full-text available
There is a growing body of evidence that marijuana use during adolescence, a critical period in neurocognitive development, may have lasting detrimental impact on executive functioning. The Ottawa Prenatal Prospective Study (OPPS) has followed participants over 20 years, from birth to young adulthood, and has collected data on potentially confounding lifestyle variables, such as prenatal drug exposure and current drug use. In the present study, we report the effects of heavy adolescent onset marijuana use on cognitive interference while performing a Counting Stroop task using fMRI in a sample of OPPS participants, while controlling for current nicotine use and prenatal marijuana exposure. Despite a lack of performance differences, the neural activity of young adults who use marijuana on a regular basis differed significantly compared to non-users while performing the task. This included increased activity in the right rolandic operculum, cerebellar tonsil, bilateral postcentral gyrus, cingulate gyrus, and right supplementary motor area. This recruitment of additional brain regions is suggestive of compensatory strategies among marijuana users in order to successfully complete the task, highlighting the impact of early marijuana use on neurocognitive development and altered brain function.
Article
Full-text available
Background Whilst cannabis use appears to be a causal risk factor for the development of schizophrenia-related psychosis, associations with mania remain relatively unknown. This review aimed to examine the impact of cannabis use on the incidence of manic symptoms and on their occurrence in those with pre-existing bipolar disorder. Methods A systematic review of the scientific literature using the PRISMA guidelines. PsychINFO, Cochrane, Scopus, Embase and MEDLINE databases were searched for prospective studies. Results Six articles met inclusion criteria. These sampled 2,391 individuals who had experienced mania symptoms. The mean length of follow up was 3.9 years. Studies support an association between cannabis use and the exacerbation of manic symptoms in those with previously diagnosed bipolar disorder. Furthermore, a meta-analysis of two studies suggests that cannabis use is associated with an approximately 3-fold (Odds Ratio: 2.97; 95% CI: 1.80 to 4.90) increased risk for the new onset of manic symptoms. Limitations We were only able to identify a small number of studies of variable quality, thus our conclusions remain preliminary. Conclusions Our findings whilst tentative, suggest that cannabis use may worsen the occurrence of manic symptoms in those diagnosed with bipolar disorder, and may also act as a causal risk factor in the incidence of manic symptoms. This underscores the importance of discouraging cannabis use among youth and those with bipolar disorder to help prevent chronic psychiatric morbidity. More high quality prospective studies are required to fully elucidate how cannabis use may contribute to the development of mania over time.
Article
Full-text available
New Mexico was the first state to list post-traumatic stress disorder (PTSD) as a condition for the use of medical cannabis. There are no published studies, other than case reports, of the effects of cannabis on PTSD symptoms. The purpose of the study was to report and statistically analyze psychometric data on PTSD symptoms collected during 80 psychiatric evaluations of patients applying to the New Mexico Medical Cannabis Program from 2009 to 2011. The Clinician Administered Posttraumatic Scale for DSM-IV (CAPS) was administered retrospectively and symptom scores were then collected and compared in a retrospective chart review of the first 80 patients evaluated. Greater than 75% reduction in CAPS symptom scores were reported when patients were using cannabis compared to when they were not. Cannabis is associated with reductions in PTSD symptoms in some patients, and prospective, placebo-controlled study is needed to determine efficacy of cannabis and its constituents in treating PTSD.
Article
Full-text available
The recreational use of cannabis can have persistent adverse effects on mental health. Delta-9-tetrahydrocannabinol (THC) is the main psychoactive constituent of cannabis, and most, if not all, of the effects associated with the use of cannabis are caused by THC. Recent studies have suggested a possible protective effect of another cannabinoid, cannabidiol (CBD). A literature search was performed in the bibliographic databases PubMed, PsycINFO, and Web of Science using the keyword "cannabidiol." After removing duplicate entries, 1295 unique titles remained. Based on the titles and abstracts, an initial selection was made. The reference lists of the publications identified in this manner were examined for additional references. Cannabis is not a safe drug. Depending on how often someone uses, the age of onset, the potency of the cannabis that is used and someone's individual sensitivity, the recreational use of cannabis may cause permanent psychological disorders. Most recreational users will never be faced with such persistent mental illness, but in some individuals cannabis use leads to undesirable effects: cognitive impairment, anxiety, paranoia, and increased risks of developing chronic psychosis or drug addiction. Studies examining the protective effects of CBD have shown that CBD can counteract the negative effects of THC. However, the question remains of how the laboratory results translate to the types of cannabis that are encountered by real-world recreational users.
Article
Full-text available
Longitudinal studies reporting the association between cannabis use and developing depression provide mixed results. The objective of this study was to establish the extent to which different patterns of use of cannabis are associated with the development of depression using meta-analysis of longitudinal studies. Method Peer-reviewed publications reporting the risk of developing depression in cannabis users were located using searches of EMBASE, Medline, PsychINFO and ISI Web of Science. Only longitudinal studies that controlled for depression at baseline were included. Data on several study characteristics, including measures of cannabis use, measures of depression and control variables, were extracted. Odds ratios (ORs) were extracted by age and length of follow-up. After screening for 4764 articles, 57 articles were selected for full-text review, of which 14 were included in the quantitative analysis (total number of subjects = 76058). The OR for cannabis users developing depression compared with controls was 1.17 [95% confidence interval (CI) 1.05-1.30]. The OR for heavy cannabis users developing depression was 1.62 (95% CI 1.21-2.16), compared with non-users or light users. Meta-regression revealed no significant differences in effect based on age of subjects and marginal difference in effect based on length of follow-up in the individual studies. There was large heterogeneity in the number and type of control variables in the different studies. Cannabis use, and particularly heavy cannabis use, may be associated with an increased risk for developing depressive disorders. There is need for further longitudinal exploration of the association between cannabis use and developing depression, particularly taking into account cumulative exposure to cannabis and potentially significant confounding factors.
Article
Full-text available
Background: Cannabis is the most prevalent illicit drug identified in impaired drivers. The effects of cannabis on driving continue to be debated, making prosecution and legislation difficult. Historically, delays in sample collection, evaluating the inactive Δ(9)-tetrahydrocannabinol (THC) metabolite 11-nor-9-carboxy-THC, and polydrug use have complicated epidemiologic evaluations of driver impairment after cannabis use. Content: We review and evaluate the current literature on cannabis' effects on driving, highlighting the epidemiologic and experimental data. Epidemiologic data show that the risk of involvement in a motor vehicle accident (MVA) increases approximately 2-fold after cannabis smoking. The adjusted risk of driver culpability also increases substantially, particularly with increased blood THC concentrations. Studies that have used urine as the biological matrix have not shown an association between cannabis and crash risk. Experimental data show that drivers attempt to compensate by driving more slowly after smoking cannabis, but control deteriorates with increasing task complexity. Cannabis smoking increases lane weaving and impaired cognitive function. Critical-tracking tests, reaction times, divided-attention tasks, and lane-position variability all show cannabis-induced impairment. Despite purported tolerance in frequent smokers, complex tasks still show impairment. Combining cannabis with alcohol enhances impairment, especially lane weaving. Summary: Differences in study designs frequently account for inconsistencies in results between studies. Participant-selection bias and confounding factors attenuate ostensible cannabis effects, but the association with MVA often retains significance. Evidence suggests recent smoking and/or blood THC concentrations 2-5 ng/mL are associated with substantial driving impairment, particularly in occasional smokers. Future cannabis-and-driving research should emphasize challenging tasks, such as divided attention, and include occasional and chronic daily cannabis smokers.
Article
Full-text available
Cannabidiol is a component of marijuana that does not activate cannabinoid receptors, but moderately inhibits the degradation of the endocannabinoid anandamide. We previously reported that an elevation of anandamide levels in cerebrospinal fluid inversely correlated to psychotic symptoms. Furthermore, enhanced anandamide signaling let to a lower transition rate from initial prodromal states into frank psychosis as well as postponed transition. In our translational approach, we performed a double-blind, randomized clinical trial of cannabidiol vs amisulpride, a potent antipsychotic, in acute schizophrenia to evaluate the clinical relevance of our initial findings. Either treatment was safe and led to significant clinical improvement, but cannabidiol displayed a markedly superior side-effect profile. Moreover, cannabidiol treatment was accompanied by a significant increase in serum anandamide levels, which was significantly associated with clinical improvement. The results suggest that inhibition of anandamide deactivation may contribute to the antipsychotic effects of cannabidiol potentially representing a completely new mechanism in the treatment of schizophrenia.
Article
Full-text available
Objective Multiple sclerosis (MS) is associated with chronic symptoms, including muscle stiffness, spasms, pain and insomnia. Here we report the results of the Multiple Sclerosis and Extract of Cannabis (MUSEC) study that aimed to substantiate the patient based findings of previous studies. Patients and methods Patients with stable MS at 22 UK centres were randomised to oral cannabis extract (CE) (N=144) or placebo (N=135), stratified by centre, walking ability and use of antispastic medication. This double blind, placebo controlled, phase III study had a screening period, a 2 week dose titration phase from 5 mg to a maximum of 25 mg of tetrahydrocannabinol daily and a 10 week maintenance phase. The primary outcome measure was a category rating scale (CRS) measuring patient reported change in muscle stiffness from baseline. Further CRSs assessed body pain, spasms and sleep quality. Three validated MS specific patient reported outcome measures assessed aspects of spasticity, physical and psychological impact, and walking ability. Results The rate of relief from muscle stiffness after 12 weeks was almost twice as high with CE than with placebo (29.4% vs 15.7%; OR 2.26; 95% CI 1.24 to 4.13; p=0.004, one sided). Similar results were found after 4 weeks and 8 weeks, and also for all further CRSs. Results from the MS scales supported these findings. Conclusion The study met its primary objective to demonstrate the superiority of CE over placebo in the treatment of muscle stiffness in MS. This was supported by results for secondary efficacy variables. Adverse events in participants treated with CE were consistent with the known side effects of cannabinoids. No new safety concerns were observed. Trial registration number NCT00552604.
Article
Full-text available
Data on the mutagenicity, developmental toxicity and carcinogenicity of cannabis are reviewed in this article. The available evidence on the possible mutagenic effects of cannabinoids is still inconclusive. There is no consensus on the induction of point mutations, while some experimental results suggest that cannabinoids may cause chromosomal damage. Concerning the developmental effects of cannabis, an increased embryolethality and somatic growth retardation have been observed in animals, as well as changes in motor behaviour, after perinatal exposure to cannabinoids. An elevated risk for infertility has been suggested for women smoking marijuana. On the other hand, intrauterine exposure to cannabinoids may be followed by changes of behaviour later in childhood. Finally, the experimental work concerning the possible carcinogenic action of cannabinoids has shown that cannabis acts as a tumour promotor in animals. Epidemiological studies have incriminated cannabis smoking for the development of head and neck carcinomas and for carcinomas of the respiratory tract in humans, but several confounding factors have rendered this evidence inconclusive. At least part of the great popularity of cannabis smoking is due to the widespread belief that it is harmless. However, the studies presented in this review show that, despite their low acute toxicity profile, cannabinoids represent several risks in terms of chronic toxicity.
Article
Full-text available
Cannabis is the most widely used illicit drug in the developed world. Despite this, there is a paucity of research examining its long-term effect on the human brain. To determine whether long-term heavy cannabis use is associated with gross anatomical abnormalities in 2 cannabinoid receptor-rich regions of the brain, the hippocampus and the amygdala. Cross-sectional design using high-resolution (3-T) structural magnetic resonance imaging. Participants were recruited from the general community and underwent imaging at a hospital research facility. Fifteen carefully selected long-term (>10 years) and heavy (>5 joints daily) cannabis-using men (mean age, 39.8 years; mean duration of regular use, 19.7 years) with no history of polydrug abuse or neurologic/mental disorder and 16 matched nonusing control subjects (mean age, 36.4 years). Volumetric measures of the hippocampus and the amygdala combined with measures of cannabis use. Subthreshold psychotic symptoms and verbal learning ability were also measured. Cannabis users had bilaterally reduced hippocampal and amygdala volumes (P = .001), with a relatively (and significantly [P = .02]) greater magnitude of reduction in the former (12.0% vs 7.1%). Left hemisphere hippocampal volume was inversely associated with cumulative exposure to cannabis during the previous 10 years (P = .01) and subthreshold positive psychotic symptoms (P < .001). Positive symptom scores were also associated with cumulative exposure to cannabis (P = .048). Although cannabis users performed significantly worse than controls on verbal learning (P < .001), this did not correlate with regional brain volumes in either group. These results provide new evidence of exposure-related structural abnormalities in the hippocampus and amygdala in long-term heavy cannabis users and corroborate similar findings in the animal literature. These findings indicate that heavy daily cannabis use across protracted periods exerts harmful effects on brain tissue and mental health.
Article
Medicolegal realities surrounding “medical marijuana” or “medical cannabis” are rapidly evolving in the United States. Clinicians are increasingly being asked by patients to share information about or certify them for medical cannabis. In order to engage in informed discussions with patients or be comfortable certifying them in states with medical cannabis laws, clinicians may benefit from an understanding of the current state of medical knowledge about medical cannabis. Intended for the generalist and subspecialist, this review provides an overview of the legal status, pharmacology, benefits, risks, and abuse liability of medical cannabis along with a general framework for counseling patients.
Article
Introduction: Cannabis is the most widely used illicit substance in the world. An increasing number of jurisdictions have legalized medical and non-medical cannabis; comparisons across jurisdictions can help evaluate the impact of these policy innovations. The current study examined patterns of cannabis use among youth in Canada (CA), England (EN) and the United States (US). At the time of study, non-medical cannabis use was prohibited federally in all three countries; however, medical cannabis was accessible with varying restrictions in CA, EN and most US states, while non-medical cannabis was legal in four US states. Methods: Data come from an international online survey conducted in July 2017 (n = 12,064). Youth, aged 16-19, were asked about cannabis consumption, perceived access to cannabis, perceptions of harm, and driving after cannabis use. All estimates represent weighted data. Results: US youth were more likely to report more frequent cannabis consumption, easier access, lower perceptions of harm, and higher rates of driving after cannabis use than CA and EN youth. CA youth reported more frequent consumption, easier access, and higher rates of driving after cannabis use than EN youth. Conclusion: CA and US youth had higher prevalence of use, easier access, lower perceived harm and higher driving rates after cannabis use in comparison to EN. These differences may reflect more permissive cannabis policies in CA and US, as well as pre-existing trends. Future waves of the international cannabis study will examine trends over time within the same countries after cannabis legalization in CA and additional US states.
Article
Introduction and Aims Cannabis use is the most widely used illicit substance in the USA. Currently, over half of US jurisdictions have legalised medical cannabis and nine US jurisdictions (and Washington DC) have legalised non‐medical cannabis. Comparisons across jurisdictions can help to evaluate the impact of these policies. The current study examined patterns of cannabis use among youth in three categories: (i) states that have legalised non‐medical cannabis with established markets; (ii) jurisdictions that recently legalised non‐medical cannabis without established markets; and (iii) all other jurisdictions where non‐medical cannabis is prohibited. Design and Methods Data come from an online survey conducted among 4097 US youth aged 16–19 recruited through a commercial panel in July/August 2017. Regression models were fitted to examine differences between regulatory categories for cannabis consumption, perceived access to cannabis, modes of use, perceptions of harm and cannabis‐impaired driving. All estimates represent weighted data. Results States that had legalised non‐medical cannabis had higher prevalence, easier access and lower driving rates than non‐legal states. There were few differences between states with established non‐medical cannabis markets and those that had recently legalised. Discussion and Conclusions Cannabis use among youth was higher in states that have legalised non‐medical cannabis, regardless of how long the policy had been implemented or whether markets had been established. This suggests that differences between states with and without legal non‐medical cannabis may partly be due to longer‐term patterns established prior and highlights the importance of longitudinal evidence to evaluate the impact of cannabis policies.
Article
Purpose: Approximately 6%-8% of U.S. adolescents are daily/past-month users of marijuana. However, survey data may not reliably reflect the impact of legalization on adolescents. The objective was to evaluate the impact of marijuana legalization on adolescent emergency department and urgent cares visits to a children's hospital in Colorado, a state that has allowed both medical and recreational marijuana. Methods: Retrospective review of marijuana-related visits by International Classification of Diseases codes and urine drug screens, from 2005 through 2015, for patients ≥ 13 and < 21 years old. Results: From 2005 to 2015, 4,202 marijuana-related visits were identified. Behavioral health evaluation was obtained for 2,813 (67%); a psychiatric diagnosis was made for the majority (71%) of these visits. Coingestants were common; the most common was ethanol (12%). Marijuana-related visits increased from 1.8 per 1,000 visits in 2009 to 4.9 in 2015. (p = < .0001) CONCLUSIONS: Despite national survey data suggesting no appreciable difference in adolescent marijuana use, our data demonstrate a significant increase in adolescent marijuana-associated emergency department and urgent cares visits in Colorado.
Article
An association between marijuana use and schizophrenia has been noted for decades, and the recent emergence of high-efficacy synthetic cannabinoids (SCBs) as drugs of abuse has lead to a growing number of clinical reports of persistent psychotic effects in users of these substances. The mechanisms underlying SCB-elicited pro-psychotic effects is unknown, but given the ubiquitous neuromodulatory functions of the endocannabinoid system, it seems likely that agonist actions at cannabinoid type-1 receptors (CB1Rs) might modulate the functions of other neurotransmitter systems known to be involved in schizophrenia. The present review surveys what is currently known about the interactions of CB1Rs with dopamine, serotonin, and glutamate systems, because all three of those neurotransmitters are well-established in the pathophysiology of schizophrenia and psychosis. Identification of molecular mechanisms underlying the pro-psychotic effects of SCB drugs of abuse may establish certain classes of these substances as particularly dangerous, guiding regulations to control availability of these drugs. Likewise, an understanding of the pharmacological interactions which lead to schizophrenia and psychosis subsequent to SCB exposure might guide the development of novel therapies to treat afflicted users.
Article
Objective: Research in both animals and humans indicates that cannabidiol (CBD) has antipsychotic properties. The authors assessed the safety and effectiveness of CBD in patients with schizophrenia. Method: In an exploratory double-blind parallel-group trial, patients with schizophrenia were randomized in a 1:1 ratio to receive CBD (1000 mg/day; N=43) or placebo (N=45) alongside their existing antipsychotic medication. Participants were assessed before and after treatment using the Positive and Negative Syndrome Scale (PANSS), the Brief Assessment of Cognition in Schizophrenia (BACS), the Global Assessment of Functioning scale (GAF), and the improvement and severity scales of the Clinical Global Impressions Scale (CGI-I and CGI-S). Results: After 6 weeks of treatment, compared with the placebo group, the CBD group had lower levels of positive psychotic symptoms (PANSS: treatment difference=-1.4, 95% CI=-2.5, -0.2) and were more likely to have been rated as improved (CGI-I: treatment difference=-0.5, 95% CI=-0.8, -0.1) and as not severely unwell (CGI-S: treatment difference=-0.3, 95% CI=-0.5, 0.0) by the treating clinician. Patients who received CBD also showed greater improvements that fell short of statistical significance in cognitive performance (BACS: treatment difference=1.31, 95% CI=-0.10, 2.72) and in overall functioning (GAF: treatment difference=3.0, 95% CI=-0.4, 6.4). CBD was well tolerated, and rates of adverse events were similar between the CBD and placebo groups. Conclusions: These findings suggest that CBD has beneficial effects in patients with schizophrenia. As CBD's effects do not appear to depend on dopamine receptor antagonism, this agent may represent a new class of treatment for the disorder.