Article

Cannabidiol in Anxiety and Sleep: A Large Case Series

January 2019
The Permanente journal 23

Authors:

Context: Cannabidiol (CBD) is one of many cannabinoid compounds found in cannabis. It does not appear to alter consciousness or trigger a "high." A recent surge in scientific publications has found preclinical and clinical evidence documenting value for CBD in some neuropsychiatric disorders, including epilepsy, anxiety, and schizophrenia. Evidence points toward a calming effect for CBD in the central nervous system. Interest in CBD as a treatment of a wide range of disorders has exploded, yet few clinical studies of CBD exist in the psychiatric literature. Objective: To determine whether CBD helps improve sleep and/or anxiety in a clinical population. Design: A large retrospective case series at a psychiatric clinic involving clinical application of CBD for anxiety and sleep complaints as an adjunct to usual treatment. The retrospective chart review included monthly documentation of anxiety and sleep quality in 103 adult patients. Main outcome measures: Sleep and anxiety scores, using validated instruments, at baseline and after CBD treatment. Results: The final sample consisted of 72 adults presenting with primary concerns of anxiety (n = 47) or poor sleep (n = 25). Anxiety scores decreased within the first month in 57 patients (79.2%) and remained decreased during the study duration. Sleep scores improved within the first month in 48 patients (66.7%) but fluctuated over time. In this chart review, CBD was well tolerated in all but 3 patients. Conclusion: Cannabidiol may hold benefit for anxiety-related disorders. Controlled clinical studies are needed.

Benefits, toxicity and current market of cannabidiol in edibles

Article

Full-text available

Jan 2022

The commercialization of products with cannabidiol (CBD) has undergone a significant increase. These products can be presented in different forms such as baked goods, gummies or beverages (such as kombucha, beer or teas, among others) using wide concentrations ranges. The use of CBD in edibles favors its consumption, for medicinal users, during the work week, avoid its possible social stigma and facilitates its transport. These products can be purchased on store shelves and online. There is a large number of specialized studies, in which the possible advantages of CBD consumption are described in the preclinical and clinical trials. it is also necessary to recognize the existence of other works revealing that the excessive consumption of CBD could have some repercussions on health. in this review, it is analyzed the composition and properties of Cannabis sativa L., the health benefits of cannabinoids (focusing on CBD), its consumption, its possible toxicological effects, a brief exposition of the extraction process, and a collection of different products that contain CBD in its composition.

Neurological Benefits, Clinical Challenges, and Neuropathologic Promise of Medical Marijuana: A Systematic Review of Cannabinoid Effects in Multiple Sclerosis and Experimental Models of Demyelination

Article

Full-text available

Feb 2022

Despite current therapeutic strategies for immunomodulation and relief of symptoms in multiple sclerosis (MS), remyelination falls short due to dynamic neuropathologic deterioration and relapses, leading to accrual of disability and associated patient dissatisfaction. The potential of cannabinoids includes add-on immunosuppressive, analgesic, neuroprotective, and remyelinative effects. This study evaluates the efficacy of medical marijuana in MS and its experimental animal models. A systematic review was conducted by a literature search through PubMed, ProQuest, and EBSCO electronic databases for studies reported since 2007 on the use of cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) in MS and in experimental autoimmune encephalomyelitis (EAE), Theiler’s murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD), and toxin-induced demyelination models. Study selection and data extraction were performed by 3 reviewers, and 28 studies were selected for inclusion. The certainty of evidence was appraised using the Cochrane GRADE approach. In clinical studies, there was low- and moderate-quality evidence that treatment with ~1:1 CBD/THC mixtures as a nabiximols (Sativex®) oromucosal spray reduced numerical rating scale (NRS) scores for spasticity, pain, and sleep disturbance, diminished bladder overactivity, and decreased proinflammatory cytokine and transcription factor expression levels. Preclinical studies demonstrated decreases in disease severity, hindlimb stiffness, motor function, neuroinflammation, and demyelination. Other experimental systems showed the capacity of cannabinoids to promote remyelination in vitro and by electron microscopy. Modest short-term benefits were realized in MS responders to adjunctive therapy with CBD/THC mixtures. Future studies are recommended to investigate the cellular and molecular mechanisms of cannabinoid effects on MS lesions and to evaluate whether medical marijuana can accelerate remyelination and retard the accrual of disability over the long term.

A Systematic Review of Cannabidiol Based Dosage Forms

Article

Full-text available

Dec 2021

Enhancing Endocannabinoid Control of Stress with Cannabidiol

Article

Full-text available

Dec 2021

The stress response is a well-defined physiological function activated frequently by life events. However, sometimes the stress response can be inappropriate, excessive, or prolonged; in which case, it can hinder rather than help in coping with the stressor, impair normal functioning, and increase the risk of somatic and mental health disorders. There is a need for a more effective and safe pharmacological treatment that can dampen maladaptive stress responses. The endocannabinoid system is one of the main regulators of the stress response. A basal endocannabinoid tone inhibits the stress response, modulation of this tone permits/curtails an active stress response, and chronic deficiency in the endocannabinoid tone is associated with the pathological complications of chronic stress. Cannabidiol is a safe exogenous cannabinoid enhancer of the endocannabinoid system that could be a useful treatment for stress. There have been seven double-blind placebo controlled clinical trials of CBD for stress on a combined total of 232 participants and one partially controlled study on 120 participants. All showed that CBD was effective in significantly reducing the stress response and was non-inferior to pharmaceutical comparators, when included. The clinical trial results are supported by the established mechanisms of action of CBD (including increased N-arachidonylethanolamine levels) and extensive real-world and preclinical evidence of the effectiveness of CBD for treating stress.

Autism and associated disorders: cannabis as a potential therapy

Article

Full-text available

Jan 2022

Autism spectrum disorder (ASD) is a group of disabilities with impairments in physical, verbal, and behavior areas. Regardless the growing frequency of autism, no medicine has been formed for the management of the ASD primary symptoms. The most frequently prescribed drugs are off-label. Therefore, there is necessity for an advance tactic for the treatment of autism. The endocannabinoid system has a central role in ruling emotion and social behaviors. Dysfunctions of the system donate to the behavioral deficits in autism. Therefore, the endocannabinoid system represents a potential target for the development of a novel autism therapy. Cannabis and associated compounds have produced substantial research attention as a capable therapy in neurobehavioral and neurological syndromes. In this review we examine the potential benefits of medical cannabis and related compounds in the treatment of ASD and concurrent disorders

Cannabidiol (CBD) in Cancer Management

Article

Full-text available

Feb 2022

Kylie Obrien

The plant Cannabis sativa has been in use medicinally for several thousand years. It has over 540 metabolites thought to be responsible for its therapeutic effects. Two of the key phytocannabinoids are cannabidiol (CBD) and tetrahydrocannabinol (THC). Unlike THC, CBD does not have potentially intoxicating effects. Preclinical and clinical research indicates that CBD has a wide range of therapeutic effects, and many of them are relevant to the management of cancer. In this article, we explore some of the potential mechanisms of action of CBD in cancer, and evidence of its efficacy in the integrative management of cancer including the side effects associated with its treatment, demonstrating its potential for integration with orthodox cancer care.

Determination of cannabinoids in hair: Indicators for illegal vs CBD-rich cannabis use

Article

Feb 2022
FORENSIC SCI INT

Cannabis products rich in cannabidiol (CBD) and low in Δ9-tetrahydrocannabinol (THC) (e.g., light cannabis in Italy) are becoming widely popular and available on the market as replacements for THC preparations and tobacco for their recreational and/or therapeutic benefits. In this paper, which aims to establish alternative discrimination parameters between hair samples from CBD-rich and THC-prevalent cannabis users, cannabinoid concentrations, such as THC, CBD, 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH) and 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC) were quantified in 127 hair samples by a GC-MS/MS technique. Initially, this analysis was able to discriminate two cohorts: cohort 1 (individuals with THC values ε 0.05 ng/mg and THC-COOH ε 0.2 pg/mg or THC-positive users, n = 60) and cohort 2 (individuals with THC values ranging between 0.01-0.05 ng/mg and THC-COOH or 11-OH-THC ε LOQs, n = 67). The evaluation of CBD/THC ratio in cohort 2 identified two further sub-cohorts 2a (CBD/THC << 1 or ~ 1, THC-prevalent cannabis users) and 2b (CBD/THC >>1, suspected CBD-rich and THC-low cannabis users). The latter showed unusual profiles for THC metabolites, in particular for 11-OH-THC. Statistical evaluation of the data of cohort 1, cohort 2a and cohort 2b yielded significant differences in CBD/THC and THC/11-OH-THC. Based on the analysis of 337 seized cannabis samples and 630 CBD-rich/light cannabis samples by GC-FID and GC-MS, respectively, we also evaluated statistical differences in the CBD/THC ratio between biological (hair) and plant-derived samples. Considering the legal implications of a positive result, the obtained findings could be relevant for the interpretation of cannabinoid concentrations in hair. Further studies are necessary to elucidate the reason behind the unusual metabolic ratios.

Insomnia treatment: a new multitasking natural compound based on melatonin and cannabis extracts

Article

Full-text available

Feb 2022

Objectives: Our main aim was to investigate the short-term thera-peutic effects, safety/tolerability of natural compound, composed of melatonin (1,5 mg) and cannabis extracts (2.5 mg CBD) in patients with sleep disorders. Methods: In this spontaneous, anecdotal, retrospective, "compas-sionate-use," observational, open-label study, 20 patients (age 43-96 years) were appealed to our "Second Opinion Medical Consulting Net-work" (Modena, Italy), because of a variable pattern of sleep disorders and anxiety and were instructed to take sublingually the compound (20 drops) overnight for 3 months of treatment. Tolerability and adverse effects were assessed monthly during the treatment period through direct contact (email or telephone) or visit if required. Results: PSQUI and HAM-A scores evidenced reduction in mood alterations, including anxiety, panic, paranoia, depression (P < 0.03), in pain (P < 0.02) and good general health perceptions. Conclusions: These data suggest that the formula CBD-melatonin could be competitive with the classic hypnotic synthetic drugs, the antioxidant activity of melatonin offers a further benefit to the brain network, restoring the biological clock functions, while CBD, redu-cing chronic pain perception, helps to complete the neuromuscular relaxation and to relieve anxiety fulfilling a very balanced sensation of wellbeing during the sleep.

Impacto clínico, terapêutico e social do canabidiol na epilepsia recorrente

Article

Full-text available

Sep 2021

Introdução: Estima-se que mais de 50 milhões de pessoas no mundo tenham diagnóstico de epilepsia, no entanto, um terço dessas pessoas não possuem a patologia controlada, apresentando quadros de convulsão e epilepsia recorrente. Desta forma, buscar novas terapêuticas antiepilépticas são necessárias, a atividade antiepiléptica dos canabinóides têm-se mostrado com grande poder terapêutico. Objetivo: Responder quais os impactos clínicos, terapêuticos e sociais do uso do canabidiol (CBD) em pacientes com epilepsia recorrente. Metodologia: Trata-se de uma revisão bibliográfica no método de revisão de integrativa de literatura, realizado entre os meses de abril e maio de 2021, nas bases de dados da MEDLINE/Pubmed e LILACS, por meio dos descritores e operador booleano “Canabidiol” AND “Epilepsia”. Localizando-se artigos publicados entre os anos de 2016 e maio de 2021. Resultados e discussões: O mecanismo de ação ainda não é bem esclarecido, mas é reconhecido sua atuação sobre as manifestações psiquiátricas e neurológicas nas fendas pré-sinápticas. A terapia associada entre CBD e as terapias convencionais para epilepsia apresentaram melhora significativa nos sintomas epilépticos, havendo relatos de melhora completa dos sintomas em até 87,5% dos pacientes. No entanto, cerca de 10% dos pacientes queixam-se de efeitos indesejáveis e desagradáveis como aumento da ansiedade, angústia, medo, tremor e sudorese excessiva durante o tratamento, dado que seu efeito é dose dependente, necessitando de atenção do prescritor para os efeitos indesejados. O impacto social é relatado pelos pacientes como melhora na qualidade de vida e laboral, dada a diminuição da frequência de eventos convulsivos. Conclusão: A terapêutica associada do CBD com a terapia convencional na epilepsia recorrente mostra-se com grandes impactos clínicos e sociais para os pacientes acometidos. No entanto, requer atenção dos prescritores para manifestações clínicas de efeitos colaterais para readequação terapêutica e seguimento. Diante disto, a importância de novos estudos terapêuticos com o CBD é estabelecida pela necessidade de compreender mecanismos de ação e atuação em demais áreas complexas cerebrais que a epilepsia atua para ajudar no tratamento de diversas manifestações desta patologia neurológica.

Schlafstörungen aus psychiatrischer SichtSleep Disorders From a Psychiatric Perspective: 2. Teil: Therapie – Prävention – Spezielle HerausforderungenPart II: Therapy—Prevention—Special Challenges

Article

Jan 2022

Manfred Müller

Sleep disorders are among the most common health problems and optional or obligatory early symptoms that are relevant to diagnosis, as well as regularly occurring accompanying symptoms of psychiatric disorders and symptoms. These so-called non-organic sleep disorders often persist beyond the current period of illness and they are a high risk factor for illness outbreaks or relapses. Despite a high rate of comorbidity, isolated sleep disorders are also independent diagnoses. In particular, insomnia, for example, in the form of problems falling asleep and staying asleep, are often initial symptoms of psychiatric disorders. Currently available diagnostic classifications of sleep disorders are the ICD-10, DSM‑V and ICSD‑3 (International Classification of Sleep Disorders). In contrast to the ICD-10 and the DSM‑V, the ICD-11 no longer classifies sleep disorders as psychiatric illnesses, but as an independent group of illnesses. Because of the close connection with psychic disorders, this should be critically discussed in the same manner as the lack of consideration of psychiatric content in the current Austrian “Specialization Curriculum in Sleep Medicine”. Furthermore, the link to addiction, suicidality, dreams, trauma, nightmares and sleep disorders in COVID-19 is dealt with.

Cannabidiol (CBD) in the Self-Treatment of Depression - Exploratory Study and a New Phenomenon of Concern for Psychiatrists

Article

Full-text available

Mar 2022

Cannabis sativa, whose flowers are also known as marijuana or marihuana, is a recreational plant that contains many chemicals that are constantly being studied by scientists around the world. One of these substances is cannabidiol (CBD), which has gained widespread popularity on the internet as a cure for mental health problems, leading many people to use CBD to self-treat depression and anxiety. This article presents an exploratory cohort study (n = 90) of a group of people aged 16-69 using CBD to self-heal depression symptoms. The survey included basic sociodemographic questionnaire and validated Hospital Depression and Anxiety Scale. And was distributed via the Internet. The results were statistically analyzed. High school degree was the most commonly held education (46%), large city was the most popular place of living (33%) and majority of the respondents have a full-time job (53%). Only 19% of the respondents consult their doctor or pharmacists about taking CBD. On the group of psychiatric patients, only 49% of respondents tell their psychiatrist about using the compound. Psychiatrists should be aware of CBD use in their patients during their daily practice, as CBD use can be found within people from all walks of life, and due to public interest, there is a need for education and research on the efficacy and safety of CBD use for mental disorders.

Mood, sleep and pain comorbidity outcomes in cannabis dependent patients: Findings from a nabiximols versus placebo randomised controlled trial

Article

Full-text available

Mar 2022
DRUG ALCOHOL DEPEN

Background Mood, sleep and pain problems are common comorbidities among treatment-seeking cannabis-dependent patients. There is limited evidence suggesting treatment for cannabis dependence is associated with their improvement. This study explored the impact of cannabis dependence treatment on these comorbidities. Methods This is a secondary analysis from a 12-week double-blind placebo-controlled trial testing the efficacy of a cannabis agonist (nabiximols) against placebo in reducing illicit cannabis use in 128 cannabis-dependent participants. Outcome measurements including DASS-21 (Depression, Anxiety, and Stress subscales); Insomnia Severity Index (ISI); and Brief Pain Inventory (BPI), were performed at weeks 0, 4, 8, 12 and 24. Each was analysed as continuous outcomes and as binary cases based on validated clinical cut-offs. Results Among those whose DASS and ISI scores were in the moderate to severe range at baseline, after controlling for cannabis use, there was a gradual decrease in severity of symptoms over the course of the trial. BPI decreased significantly until week 12 and then rose again in the post-treatment period during weeks 12-24. Neither pharmacotherapy type (nabiximols vs placebo) nor number of counselling sessions contributed significant explanatory power to any of the models and were excluded from the final analyses for both continuous and categorical outcomes. Conclusions Participants in this trial who qualified as cases at baseline had elevated comorbidity symptoms. There was no evidence that nabiximols treatment is a barrier to achieving reductions in the comorbid symptoms examined. Cannabis dependence treatment reduced illicit cannabis use and improved comorbidity symptoms, even when complete abstinence was not achieved.

Cannabidiol Inhibits Tumorigenesis in Cisplatin-Resistant Non-Small Cell Lung Cancer via TRPV2

Article

Full-text available

Feb 2022

Chemotherapy forms the backbone of current treatments for many patients with advanced non-small-cell lung cancer (NSCLC). However, the survival rate is low in these patients due to the development of drug resistance, including cisplatin resistance. In this study, we developed a novel strategy to combat the growth of cisplatin-resistant (CR) NSCLC cells. We have shown that treatment with the plant-derived, non-psychotropic small molecular weight molecule, cannabidiol (CBD), significantly induced apoptosis of CR NSCLC cells. In addition, CBD treatment significantly reduced tumor progression and metastasis in a mouse xenograft model and suppressed cancer stem cell properties. Further mechanistic studies demonstrated the ability of CBD to inhibit the growth of CR cell lines by reducing NRF-2 and enhancing the generation of reactive oxygen species (ROS). Moreover, we show that CBD acts through Transient Receptor Potential Vanilloid-2 (TRPV2) to induce apoptosis, where TRPV2 is expressed on human lung adenocarcinoma tumors. High expression of TRPV2 correlates with better overall survival of lung cancer patients. Our findings identify CBD as a novel therapeutic agent targeting TRPV2 to inhibit the growth and metastasis of this aggressive cisplatin-resistant phenotype in NSCLC.

Magnitude of Substance Use and Its Associated Factors Among the Medical Students in India and Implications for Medical Education: A Narrative Review

Article

Full-text available

Aug 2021
Indian J Psychol Med

Background Medical students are at an increased risk of developing substance use and related problems (SURP) because of the inherent stress associated with the professional medical course apart from the developmental risk factors. However, this is under-researched. Moreover, a comprehensive review on the prevalence of SURP among the medical undergraduates (UGs) and associated factors is lacking from India. To fill this gap, the current research work is aimed to review the existing literature on the magnitude of the SURP among UGs of India and its determinants. Methods PubMed, Medline, and Google Scholar databases were searched for the original articles studying the prevalence of SURP among medical UGs of India, published from inception till date. Non-original articles, studies on behavioral addictions, and those not directly assessing the prevalence of SURP among the medical UGs were excluded. Results A total of 39 studies were found eligible for the review. Alcohol (current use: 3.2%–43.8%), followed by tobacco (3.7%–28.8%) and cannabis (1.6%–15%), were the common substances used by the medical students. Among the females, an increasing trend of substance use, particularly of nonprescription sedatives (even higher than males), alcohol, and smoking, was seen. Family history, peer pressure, transition from school to college life, and progression in the medical course were important associated factors. Conclusion Sensitizing medical students and college authorities, increasing the duration of training on SURP in medical curricula, and providing psychological support for the students with SURP could address this issue.

Cannabidiol (CBD) in Rheumatic Diseases (Musculoskeletal Pain)

Article

Full-text available

Jul 2022
Curr Rheumatol Rep

Purpose of Review This review will address the many uncertainties surrounding the medical use of cannabidiol (CBD). We will begin with an overview of the legal and commercial environment, examine recent preclinical and clinical evidence on CBD, explore questions concerning CBD raised by healthcare professionals and patients, investigate dosing regimens and methods of administration, and address current challenges in the accumulation of sound evidence. Recent Findings CBD has potential for relief of symptoms of pain, sleep, and mood disturbance in rheumatology patients, but sound clinical evidence is lacking. CBD is safe when accessed from a regulated source, whereas wellness products are less reliable regarding content and contaminants. Dosing for symptom relief has not yet been established. Summary As many rheumatology patients are trying CBD as a self-management strategy, the healthcare community must urgently accrue sound evidence for effect.

In the weeds: a retrospective study of patient interest in and experience with cannabis at a cancer center

Article

Full-text available

Jun 2022
SUPPORT CARE CANCER

Background Cannabis products, including the cannabinoids CBD and THC, are rising in popularity and increasingly used for medical purposes. While there is some evidence that cannabinoids improve cancer-associated symptoms, understanding regarding appropriate use remains incomplete. Purpose To describe patient experiences with medical cannabis with focus on use contexts and patients’ reported benefits and harms. Methods A standardized intake form was implemented in a dedicated medical cannabis clinic at an NCI-designated cancer center; data from this form was abstracted for all initial visits from October 2019 to October 2020. We report descriptive statistics, chi-square analysis, and multivariate logistic regression. Results Among 163 unique new patients, cannabis therapy was commonly sought for sleep, pain, anxiety, and appetite. Twenty-nine percent expressed interest for cancer treatment; 40% and 46% reported past use of CBD and THC, respectively, for medical purposes. Among past CBD users, the most commonly reported benefits were less pain (21%) or anxiety (17%) and improvement in sleep (15%); 92% reported no side effects. Among those with past THC use, reported benefits included improvement in appetite (40%), sleep (32%), nausea (28%), and pain (17%); side effects included feeling “high.” Seeking cannabis for anti-neoplastic effects was associated with receipt of active cancer treatment in both univariate and multivariate analysis. Conclusion Cancer patients seek medical cannabis to address a wide variety of concerns despite insufficient evidence of benefits and harms. As more states move to legalize medical and recreational cannabis, cancer care providers must remain aware of emerging data and develop knowledge and skills to counsel their patients about its use.

Determination of Heavy Metals in Cannabinoid-Based Food Products Using Microwave-Assisted Digestion and ICP-MS

Article

Full-text available

May 2022
FOOD ANAL METHOD

A microwave-assisted digestion using only diluted nitric acid for the determination of 14 heavy metals including As, Cd, Hg, and Pb in cannabinoid-based food products using ICP-MS was developed and validated. Cannabinoid-based liquid beverage, powdered beverage, chocolate, and tea samples were digested using different nitric acid concentrations (20, 30, 40, 50, and 100% (v/v) HNO3) and evaluated for digestion efficiency using spike recovery studies. Spike recoveries for As, Cd, Hg, and Pb were all within 81–114% for all acid concentrations; hence, the use of 20% (v/v) HNO3 was selected in view of lower reagent consumption, lower dilution factors, and reduced spectral interferences associated with residual acidity. The developed method was further validated by detection limit, precision, and accuracy. Results showed that the proposed method was highly sensitive with detection limits within parts-per-trillion (ng L–1) levels. Notably, detection limits for Hg were within 2 to 10 ng L–1, making the proposed method comparable to other mercury detection methods. Furthermore, the recovery of majority of the metals analyzed is within 80–120% indicating good accuracy. Finally, the developed method was also applicable to samples with complex matrices such as chocolates. Therefore, it can potentially be used for routine analysis of heavy metals in cannabinoid-based products.

The Endocannabinoids-Microbiota Partnership in Gut-Brain Axis Homeostasis: Implications for Autism Spectrum Disorders

Article

Full-text available

Jun 2022

The latest years have witnessed a growing interest towards the relationship between neuropsychiatric disease in children with autism spectrum disorders (ASD) and severe alterations in gut microbiota composition. In parallel, an increasing literature has focused the attention towards the association between derangement of the endocannabinoids machinery and some mechanisms and symptoms identified in ASD pathophysiology, such as alteration of neural development, immune system dysfunction, defective social interaction and stereotypic behavior. In this narrative review, we put together the vast ground of endocannabinoids and their partnership with gut microbiota, pursuing the hypothesis that the crosstalk between these two complex homeostatic systems (bioactive lipid mediators, receptors, biosynthetic and hydrolytic enzymes and the entire bacterial gut ecosystem, signaling molecules, metabolites and short chain fatty acids) may disclose new ideas and functional connections for the development of synergic treatments combining “gut-therapy,” nutritional intervention and pharmacological approaches. The two separate domains of the literature have been examined looking for all the plausible (and so far known) overlapping points, describing the mutual changes induced by acting either on the endocannabinoid system or on gut bacteria population and their relevance for the understanding of ASD pathophysiology. Both human pathology and symptoms relief in ASD subjects, as well as multiple ASD-like animal models, have been taken into consideration in order to provide evidence of the relevance of the endocannabinoids-microbiota crosstalk in this major neurodevelopmental disorder.

Generalized Anxiety Disorder 7-Item (GAD-7) Scores in Medically Authorized Cannabis Patients—Ontario and Alberta, Canada

Article

Full-text available

Sep 2021

Objectives Despite increasing rates of legalization of medical cannabis worldwide, the current evidence available on its effect on mental health outcomes including anxiety is of mixed results. This study assesses the effect of medical cannabis on generalized anxiety disorder 7-item (GAD-7) scores in adult patients between 2014 and 2019 in Ontario and Alberta, Canada. Methods An observational cohort study of adults authorized to use medical cannabis. The GAD-7 was administered at the time of the first visit to the clinic and subsequently over the follow-up time period of up to 3.2 years. Overall changes in GAD-7 scores were computed (mean change) and categorized as: no change (<1 point); improvement; or worsening—over time. Results A total of 37,303 patients had initial GAD-7 scores recorded and 5,075 (13.6%) patients had subsequent GAD-7 follow-up scores. The average age was 54.2 years (SD 15.7 years), 46.0% were male, and 45.6% noted anxiety symptoms at the baseline. Average GAD-7 scores were 9.11 (SD 6.6) at the baseline and after an average of 282 days of follow-up (SD 264) the average final GAD-7 score recorded was 9.04 (SD 6.6): mean change −0.23 (95% CI, −0.28 to −0.17, t[5,074]: −8.19, p-value <0.001). A total of 4,607 patients (90.8%) had no change in GAD-7 score from their initial to final follow-up, 188 (3.7%) had a clinically significant decrease, and 64 (1.3%) noted a clinically significant increase in their GAD-7 scores. Conclusions Overall, there was a statistically significant decrease in GAD-7 scores over time (in particular, in the 6–12-month period). However, this change did not meet the threshold to be considered clinically significant. Thus, we did not detect clinical improvements or detriment in GAD-7 scores in medically authorized cannabis patients. However, future well-controlled clinical trials are needed to fully examine risks or benefits associated with using medical cannabis to treat anxiety conditions.

An Electrochemical Sensor Based on Amino Magnetic Nanoparticle-Decorated Graphene for Detection of Cannabidiol

Article

Full-text available

Aug 2021

For detection of cannabidiol (CBD)—an important ingredient in Cannabis sativa L.—amino magnetic nanoparticle-decorated graphene (Fe3O4-NH2-GN) was prepared in the form of nanocomposites, and then modified on a glassy carbon electrode (GCE), resulting in a novel electrochemical sensor (Fe3O4-NH2-GN/GCE). The applied Fe3O4-NH2 nanoparticles and GN exhibited typical structures and intended surface groups through characterizations via transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray powder diffraction (XRD), vibrating sample magnetometer (VSM), and Raman spectroscopy. The Fe3O4-NH2-GN/GCE showed the maximum electrochemical signal for CBD during the comparison of fabricated components via the cyclic voltammetry method, and was systematically investigated in the composition and treatment of components, pH, scan rate, and quantitative analysis ability. Under optimal conditions, the Fe3O4-NH2-GN/GCE exhibited a good detection limit (0.04 μmol L−1) with a linear range of 0.1 μmol L−1 to 100 μmol L−1 (r2 = 0.984). In the detection of CBD in the extract of C. sativa leaves, the results of the electrochemical method using the Fe3O4-NH2-GN/GCE were in good agreement with those of the HPLC method. Based on these findings, the proposed sensor could be further developed for the portable and rapid detection of natural active compounds in the food, agricultural, and pharmaceutical fields.

Depression

Chapter

Jan 2021

Overview of Medicinal Cannabis

Chapter

Jan 2021

Routes of Administration, Pharmacokinetics and Safety of Medicinal Cannabis

Chapter

Oct 2021

There are four main routes of administration of medicinal cannabis: inhalation, the oral route, topical applications and ‘other routes’ (eg. suppositories, intranasal delivery). Each is associated with different onsets of action and durations of action due to their pharmacokinetic profiles. There are some safety issues associated with cannabis. Many of the safety concerns such as associations between cannabis use and conditions such as cannabis use disorder and various mental health conditions that have been raised in the literature relate to recreational smoking of cannabis. Cannabis is associated with a range of negative side effects that are typically dose-dependent, most of which relate to the tetrahydrocannabinol (THC) component. Cannabidiol (CBD) has less serious side effects than THC. In general, CBD has been found to be well tolerated and safe and does not cause addiction. Both CBD and THC can potentially interact with a range of pharmaceuticals because they are metabolised by many of the cytochrome P450 enzymes that metabolise pharmaceuticals. Clinical trials in epilepsy in which high doses of CBD are used in conjunction with typically several anti-epileptic medications have demonstrated that side effects can occur with certain drugs. However, whether drug-cannabis interactions are common in clinical practice has not been well established.

Insomnia

Chapter

Oct 2021

Good sleep is vital for good health, and poor sleep, in particular insomnia, is associated with a range of poor health outcomes. Sleep disorders are common and a key reason why people self-medicate with cannabis. We have two key biological mechanisms which work together to regulate our sleep-wake cycle, the processes of sleep-wake homeostasis and our circadian rhythms. The endocannabinoid system is involved in the circadian sleep-wake cycle, including maintenance and promotion of sleep, and may provide the link between the circadian regulation systems and the physiological process of sleep. Cannabis has been used for centuries to treat sleep disorders. Preclinical and clinical evidence indicate that cannabidiol and tetrahydrocannabinol may have a role to play in the treatment of sleep disorders.

Effects of alcohol, caffeine, and cannabidiol on sleep

Chapter

Jan 2021

Alcohol and caffeine are widely used legal drugs across the world which are principally used in social and recreational contexts. There is a large literature that has documented the effects of alcohol and caffeine on sleep and daytime alertness. While at low doses they initially improve sleep (alcohol) or daytime alertness (caffeine), ultimately they both disrupt either the initiation, maintenance, or staging of sleep and diminish daytime alertness. Cannabidiol is one of the two most biologically active compounds of the cannabis plant. It's use has increased over the last five years and is primarily used for its medicinal effects, among them insomnia. While now legal (2018) in the US, it falls under varying governmental controls in other countries across the world. The literature on the effect of cannabidiol on sleep, either beneficial or disruptive, is very limited. Further clarification of the risks versus benefits of these three widely used substances will improve our understanding of their effects on sleep and daytime alertness and strengthen public health guidance and messaging.

Anxiety

Chapter

Oct 2021

Anxiety is a common condition for which people have been found to self-medicate with cannabis. Anxiety is often comorbid with other conditions, including depression, sleep disorders and chronic pain. The pathomechanisms underpinning anxiety are complex. Animal and human research indicates that the endocannabinoid system is involved in our stress response and in anxiety. Evidence from preclinical studies has elucidated some of the potential mechanisms by which cannabidiol (CBD) is anxiolytic. Clinical research also supports the notion that CBD is anxiolytic, though the majority of studies have been studies of acute use rather than chronic use. There is evidence that tetrahydrocannabinol (THC) may have a bimodal effect, being anxiolytic in lower doses and anxiogenic in higher doses. The majority of studies of CBD and THC, in particular in animal studies, have utilised purified CBD or THC. Whole plant medicines that contain multiple phytocannabinoids, terpenes, polyphenols, flavonoids and other plant nutrients appear to act more potently, with different pharmacophysiologic relationships and reduced adverse effect profiles than purified isolates.

Autism Spectrum Disorder

Chapter

Oct 2021

Autism spectrum disorder (ASD) is a complex behavioral condition that is characterized by deficits in communication and social interaction, stereotypic or repetitive behaviors, restricted patterns of interest, and sensory issues including extreme responses. It begins in early childhood and extends throughout life. It is associated with several comorbidities including anxiety, depression, seizures, sleep disorders, psychosis, metabolic disorders, and others, as well as premature mortality. The etiology and pathogenesis of ASD are complex and involve altered neurodevelopment during early pregnancy. Genetic and environmental factors are involved, as are altered development of neural connectivity, mutations in genes, inflammation, immune system dysregulation, and abnormal endocannabinoid tone and signaling. The endocannabinoid system is involved in the modulation of many cellular functions and molecular pathways altered in ASD. This chapter will present an overview of the etiology and pathogenesis of ASD with a focus on how the endocannabinoid system is involved. It will then discuss the scientific evidence for why cannabidiol (CBD) shows promise in the treatment of ASD.

The current understanding of the benefits, safety, and regulation of cannabidiol in consumer products

Article

Oct 2021

The popularity of cannabidiol (CBD) in consumer products is soaring as consumers are using CBD for general health and well-being as well as to seek relief from ailments especially pain, inflammation, anxiety, depression, and sleep disorders. However, there is limited data currently in the public domain that provide support for these benefits. By contrast, a significant amount of safety evaluation data for CBD has been obtained recently from pre-clinical and clinical studies of the CBD therapeutic Epidiolex®. Yet some key data gaps concerning the safe use of CBD still remain. Furthermore, current regulations on CBD use in consumer products remain uncertain and often conflict between the state and federal level. In light of the rapidly expanding popularity of CBD-related products in the marketplace, here we review the current understanding of the benefits, safety, and regulations surrounding CBD in consumer products. This review does not advocate for or against the use of CBD in consumer products. Rather this review seeks to assess the state-of-the-science on the health effects and safety of CBD, to identify critical knowledge gaps for future studies, and to raise the awareness of the current regulations that govern CBD use in consumer products.

Immune

Chapter

Oct 2021

The focus of integrative care for the various challenges to the aging immune system starts with comprehensive preventative care: addressing overall gut health (Magrone T, Jirillo E, Immun Ageing 10(1):31, 2013); addressing nutrient deficiencies such as vitamins A, D, and E, zinc, and selenium (Kaur D, Rasane P, Singh J, Kaur S, Kumar V, Mahato DK, et al. Curr Aging Sci 12(1):15–27, 2019); encouraging a nutrient-dense diet void of inflammatory convenience foods such as packaged snacks, fried foods, and sweets; (Kiecolt-Glaser JK, Psychosom Med 72(4):365–369, 2010) and engaging in regular physical activity (Senchina DS, Kohut ML. Immunological outcomes of exercise in older adults. Clin Interv Aging. 2007;2(1):3–16). While this is applicable advice for all of us, the natural decline in immune functioning in the elder population, immunosenescence, which affects both innate and adaptive immunity, makes immune health a weakness in this population that can have dire consequences (Denkinger MD, Leins H, Schirmbeck R, Florian MC, Geiger H, Trends Immunol 36(12):815–824, 2015). Immunosenescence includes impairment of natural killer cell response to circulating cytokines, reduction in naive B- and T-cell production in the bone marrow and thymus, and sluggish maturation of lymphocytes in secondary lymphoid tissue. As a result, the elderly’s response to both novel and previously encountered antigens is ineffective. For example, individuals over 70 years old are at increased risk of influenza, in large part exacerbated by their ineffective response to vaccination (Montecino-Rodriguez E, Berent-Maoz B, Dorshkind K, J Clin Invest 123(3):958–965, 2013). As a consequence, the incidence and prevalence of allergies, autoimmune disease, and acute infections are increased in older adults (Fuentes E, Fuentes M, Alarcón M, Palomo I, An Acad Bras Cienc 89(1):285–299, 2017).

Translation of animal endocannabinoid models of PTSD mechanisms to humans: Where to next?

Article

Nov 2021
NEUROSCI BIOBEHAV R

The endocannabinoid system is known to be involved in mechanisms relevant to PTSD aetiology and maintenance, though this understanding is mostly based on animal models of the disorder. Here we review how human paradigms can successfully translate animal findings to human subjects, with the view that substantially increased insight into the effect of endocannabinoid signalling on stress responding, emotional and intrusive memories, and fear extinction can be gained using modern paradigms and methods for assessing the state of the endocannabinoid system in PTSD.

Psychological and Sleep

Chapter

Oct 2021

The mental health of the older adult population requires the practitioner to invest time in understanding the life events and lifestyle of their patients in order to adequately assess and support this key area of health. Older adults often find themselves in highly stressful environments. Big life stresses such as the loss of a spouse or loved ones, financial strain, health concerns, polypharmacy, and social isolation are common and can trigger imbalances in mental health. Even in patients with previously well-managed psychological conditions, medications begin to fail, new triggers create a higher need, and additional compromise in health ignites a mental health crisis. Complementing psychotherapy with nutritional improvements, well-placed nutraceuticals, and safe movement such as Tai Chi or swimming addresses the root causes of symptoms. Paying attention to the interconnection between brain health and gut health is critical to addressing the root causes driving the inflammation, toxicity, and hormonal imbalances that lay the foundation for psychological distress. Recognizing the bidirectional information highway between the gut and the brain, the enteric nervous system with the longest nerve in the body called the vagus nerve, is the key to understanding the interconnectedness of the two and, thus, supporting healing in the seat of our psychological state, the brain. The manifestations of various imbalances in the gut, inflammatory responses, and detoxification pathways can manifest as psychological distress. The most common psychological disorders in the aging adult population are depression, anxiety, and insomnia.

Term and Sentiment Analysis of Cannabidiol: An Infodemiological Examination of Personal and Commercial Tweets (Preprint)

Article

Jan 2021
J MED INTERNET RES

Background: In the absence of official clinical trial information, data from social networks can be used by public health and medical researchers to assess public claims about loosely regulated substances such as cannabidiol (CBD). For example, this can be achieved by comparing the medical conditions targeted by those selling CBD against the medical conditions patients commonly treat with CBD. Objective: The objective of this study was to provide a framework for public health and medical researchers to use for identifying and analyzing the consumption and marketing of unregulated substances. Specifically, we examined CBD, which is a substance that is often presented to the public as medication despite complete evidence of efficacy and safety. Methods: We collected 567,850 tweets by searching Twitter with the Tweepy Python package using the terms "CBD" and "cannabidiol." We trained two binary text classifiers to create two corpora of 167,755 personal use and 143,322 commercial/sales tweets. Using medical, standard, and slang dictionaries, we identified and compared the most frequently occurring medical conditions, symptoms, side effects, body parts, and other substances referenced in both corpora. In addition, to assess popular claims about the efficacy of CBD as a medical treatment circulating on Twitter, we performed sentiment analysis via the VADER (Valence Aware Dictionary for Sentiment Reasoning) model on the personal CBD tweets. Results: We found references to medically relevant terms that were unique to either personal or commercial CBD tweet classes, as well as medically relevant terms that were common to both classes. When we calculated the average sentiment scores for both personal and commercial CBD tweets referencing at least one of 17 medical conditions/symptoms terms, an overall positive sentiment was observed in both personal and commercial CBD tweets. We observed instances of negative sentiment conveyed in personal CBD tweets referencing autism, whereas CBD was also marketed multiple times as a treatment for autism within commercial tweets. Conclusions: Our proposed framework provides a tool for public health and medical researchers to analyze the consumption and marketing of unregulated substances on social networks. Our analysis showed that most users of CBD are satisfied with it in regard to the condition that it is being advertised for, with the exception of autism.

Assessing Efficacy and Use Patterns of Medical Cannabis for Symptom Management in Elderly Cancer Patients

Article

Jun 2022

Objectives Our study sought to further characterize patterns of medical cannabis use in elderly cancer patients. Furthermore, we sought to assess efficacy of medical cannabis for the treatment of pain, nausea, anorexia, insomnia and anxiety in elderly cancer patients. Background Medical cannabis use is growing for symptom management in cancer patients, but limited data exists on the safety or efficacy of use in elderly patients. Methods A retrospective chart review assessing changes in numerical symptom scores reported at clinic visits before and after medical cannabis initiation. Results There was no statistically significant difference in pain, nausea, appetite, insomnia or anxiety scores reported before and after initiation of medical cannabis. Oil was the most common form used, followed by vape, and the most common ratios used were high tetrahydrocannabinol (THC) to cannabidiol (CBD) and equal parts THC/CBD products. Conclusion This study did not find a statistically significant change in symptom scores with medical cannabis use, although further study is warranted given the limitations of the present study. Elderly patients most commonly are using equal parts THC/CBD or high THC ratio products initially.

Palmitoylethanolamide: A Potential Alternative to Cannabidiol

Article

Nov 2021

The endocannabinoid system (ECS) is a widespread cell signaling network that maintains homeostasis in response to endogenous and exogenous stressors. This has made the ECS an attractive therapeutic target for various disease states. The ECS is a well-known target of exogenous phytocannabinoids derived from cannabis plants, the most well characterized being Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD). However, the therapeutic efficacy of cannabis products comes with a risk of toxicity and high abuse potential due to the psychoactivity of THC. CBD, on the other hand, is reported to have beneficial medicinal properties including analgesic, neuroprotective, anxiolytic, anticonvulsant, and antipsychotic activities, while apparently lacking the toxicity of THC. Nevertheless, not only is the currently available scientific data concerning CBD’s efficacy insufficient, there is also ambiguity surrounding its regulatory status and safety in humans that brings inherent risks to manufacturers. There is a demand for alternative compounds combining similar effects with a robust safety profile and regulatory approval. Palmitoylethanolamide (PEA) is an endocannabinoid-like lipid mediator, primarily known for its anti-inflammatory, analgesic and neuroprotective properties. It appears to have a multi-modal mechanism of action, by primarily activating the nuclear receptor PPAR-α while also potentially working through the ECS, thus targeting similar pathways as CBD. With proven efficacy in several therapeutic areas, its safety and tolerability profile and the development of formulations that maximize its bioavailability, PEA is a promising alternative to CBD.

Public health for paediatricians: 15-minute guide to identify and address food insecurity

Article

Full-text available

Feb 2022

Food insecurity is a major problem in the UK. It has been both highlighted and exacerbated by the COVID-19 pandemic, and particularly affects children and young people (CYP). The effects of inadequate nutrition manifest themselves in all stages of child development and adversely affect health and educational outcomes. Healthcare professionals working with CYP can address food insecurity at individual, local community, organisational and national levels. The government plays an important role in monitoring and responding to food insecurity, supporting CYP most in need. This paper summarises how food insecurity can be identified and approached by healthcare professionals in clinical consultations, including the use of screening tools and awareness of risk factors that signpost family food insecurity. Examples of services and clinician-assisted referrals to support vulnerable patients are provided, alongside suggested methods to implement further education for the multidisciplinary healthcare team.

Multifaceted Stigma Associated with Cannabis Use in Epilepsy Treatments

Article

Full-text available

Dec 2021

Historical evidence highlights the benefits of cannabis. Between the 19th and 20th centuries, manufacturing and consumption of cannabis spiked and dwindled due to unwarranted stigma, leading to the international prohibition and reduced use of cannabis and related products, even for medicinal uses. Clinical trials and reviews of the CBD- based therapeutics showed significant evidence that these therapies are successful in reducing the frequency of seizures. Upon review of different historical texts and recent surveys, we found that the increase of education and clinical studies led to an overall decreased generalized stigma surrounding the use of cannabis and certain components of it.There has been more research on its potential for significant medical application

Medicinal Cannabis and Central Nervous System Disorders

Article

Full-text available

Apr 2022

Cannabinoids, including those found in cannabis, have shown promise as potential therapeutics for numerous health issues, including pathological pain and diseases that produce an impact on neurological processing and function. Thus, cannabis use for medicinal purposes has become accepted by a growing majority. However, clinical trials yielding satisfactory endpoints and unequivocal proof that medicinal cannabis should be considered a frontline therapeutic for most examined central nervous system indications remains largely elusive. Although cannabis contains over 100 + compounds, most preclinical and clinical research with well-controlled dosing and delivery methods utilize the various formulations of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), the two most abundant compounds in cannabis. These controlled dosing and delivery methods are in stark contrast to most clinical studies using whole plant cannabis products, as few clinical studies using whole plant cannabis profile the exact composition, including percentages of all compounds present within the studied product. This review will examine both preclinical and clinical evidence that supports or refutes the therapeutic utility of medicinal cannabis for the treatment of pathological pain, neurodegeneration, substance use disorders, as well as anxiety-related disorders. We will predominately focus on purified THC and CBD, as well as other compounds isolated from cannabis for the aforementioned reasons but will also include discussion over those studies where whole plant cannabis has been used. In this review we also consider the current challenges associated with the advancement of medicinal cannabis and its derived potential therapeutics into clinical applications.

THE EFFECTS OF CANNABIS SATIVA HYDROEXTRACTS ON TRITICUM AESTIVUM SEEDLINGS PIGMENT CONCENTRATIONS

Article

Full-text available

Jan 2021

Cannabis, or hemp, is a plant with a huge medical and economic potential. Known since ancient times, Cannabis is rich in cannabinoids of which cannabidiol (CBD) is the most biologically active compound with almost none of the negative aspects of its fellow cannabinoids. Since the 19th century, Cannabis has been used as an analgesic, anesthetic, antidepressant, sedative and even antibiotic. However, its bio-industrial potential has not yet been fully explored and given that Cannabis plants are harvested for hemp, animal feed and various agricultural purposes, their potential effects as fertilizer or herbicide have not yet been identified. This paper presents the effects of C. sativa hydroextract on Triticum aestivum seedlings. During this study it was observed that Triticum aestivum seedlings treated with 100%, 10% and 5% C. sativa extracts showed lower levels of Chlorophyll A and B than the control sample. The seedlings treated with 50% and 25% C. sativa extracts showed higher levels of Chlorophyll A and lower content of Chlorophyll B when compared to the control. There was an increase in the carotenoids detected in all samples, with 50% and 25% showing the highest levels. This suggests that C. sativa extracts have the ability to increase the carotenoids levels in T. aestivum seedlings and modify the amount of Chlorophyll A and Chlorophyll B extract in a dose-dependent manner.

Cannabinoids and sleep

Chapter

Jan 2022

Cannabis or marijuana is comprised of over 100 known sub-chemicals or cannabinoids. Two of these, delta-9-Tehtrahydrocannabinol (THC) and cannabidiol (CBD), have received increasing scrutiny regarding their effects on sleep-wake physiology and their potential for treating a wide variety of sleep disorders. The limited data available suggest there may be initial improvement in several sleep parameters but also a tendency toward tolerance with long-term use. Withdrawal effects following chronic use can be significant. There is presently little high-quality evidence currently available on the remedial properties of cannabinoids for primary sleep disorders. Large-scale, randomized, controlled studies in humans are needed.

Herbal Anxiolytics: Sources and Their Preparation Methods

Article

Mar 2022

The Use of Medical Cannabis in Clinical Practice

Article

Dec 2021

Arianne Kryskow

Medical Cannabis is receiving renewed interest in clinical practice due to the gradual increase over the last few decades of cannabis legalization and high-quality research on the potential benefits of cannabis for treating a variety of conditions (NASEM, 2017; Nursing Care of the Patient, 2018). However, the pace of medical cannabis legalization and research are outpacing the training for medical providers, leaving gaps in their confidence and ability to safely guide patients using medical cannabis (NCSBN, 2018). Medical providers are increasingly fielding questions from patients regarding the use of medical cannabis for conditions commonly seen in clinical practice, but many are uncertain of if and how they should guide patients on this use. The aim of this research is two-fold: to assess current barriers to medical providers discussing medical cannabis with their patients; and to assess the impact a one-hour educational presentation can have on addressing these barriers and increasing the likelihood of providers engaging in discussions. Though the results of this research may be limited by the small sample size surveyed, they could highlight barriers present in clinical practice and indicate possible areas for future research in expanding cannabis education for medical providers.

A narrative review of molecular mechanism and therapeutic effect of Cannabidiol (CBD)

Article

Jan 2022

Cannabidiol (CBD) is an abundant non-psychoactive phytocannabinoid in Cannabis extracts which has high affinity on a series of receptors, including type 1 cannabinoid receptor (CB1), type 2 cannabinoid receptor (CB2), GPR55, transient receptor potential vanilloid (TRPV), and peroxisome proliferator-activated receptor gamma (PPARγ). By modulating the activities of these receptors, CBD exhibits multiple therapeutic effects, including neuroprotective, antiepileptic, anxiolytic, antipsychotic, anti-inflammatory, analgesic and anti-cancer properties. CBD could also be applied to treat or prevent COVID-19 and its complications. Here, we provide a narrative review of CBD's applications in human diseases: from mechanism of action to clinical trials.

Superlatives in news articles reporting non-FDA approved indications for use of cannabis and cannabis products with a focus on psychiatric disorders: a cross-sectional analysis

Article

Nov 2021

The exaggerated language used in news articles to describe the benefits of cannabis for conditions without FDA indications may mislead the public and healthcare providers. Thus, this study's objective was to investigate the use of exaggerated language in news articles focused on cannabis and cannabis-derived products. Using a cross-sectional study design, we searched Google News from March 3, 2020, and September 3, 2019 for 11 prespecified superlative terms along with the search terms “cannabis,” “cannabidiol,” “pot,” “marijuana,” “weed,” and “CBD.” Articles were evaluated for these exaggerative terms describing cannabis and cannabis-derived products along with additional news article characteristics. Screening and data extraction occurred in a masked, duplicate fashion. We identified 612 superlative terms in 374 different news articles focused on cannabis and cannabis-derived products from 262 news outlets. Only 26 (of 374, 7.0%) news articles provided clinical data. In total, superlative terms were used to describe cannabis and cannabis-derived products for the treatment of 91 medical conditions, of which only 2 are FDA approved. The most common psychiatric disorder indicated was anxiety disorder appearing in 88 news articles. Superlatives in news articles covering the treatment of psychiatric illnesses with cannabis and cannabis-derived products are common.

Cannabis Use in a Cohort of Healthcare-Seeking United States Military Veterans With Persisting Symptoms After Mild Traumatic Brain Injury: Preliminary Observations

Article

Jan 2022

Introduction Cannabis products, including cannabidiol (CBD) and tetrahydrocannabinol (THC), are increasingly easy to procure and use across the United States. The 2018 National Survey on Drug Use and Health (NSDUH) reported a past-month cannabis use rate of 8.6% among adults 26 years of age or older in the U.S. general population. Cannabis use is commonly reported by U.S. Military Veterans with histories of mild traumatic brain injury (mTBI) receiving services at the Marcus Institute for Brain Health (MIBH), a specialty interdisciplinary clinic serving this population. The aims of this study are to describe the frequency and characteristics of cannabis product use among Veterans evaluated at MIBH and to compare the rate of cannabis use in this group to that in the general and Veteran populations reported in the 2018 NSDUH. Materials and Methods Study data were collected as part of MIBH clinical assessments between January 2018 and December 2019, which included the evaluation of the current use of cannabis products. Affirmative cannabis use responses were clarified with inquiries about the frequency of use, method of administration, product ingredients (i.e., THC and/or CBD), and reason(s) for use. Results Among 163 MIBH patients (92.6% male), 72 (44.2%) endorsed cannabis product use during the month preceding the clinical assessment. Cannabis users were significantly younger than nonusers. The frequency of past-month cannabis use was significantly greater than that reported in the comparably aged NSDUH survey general and Veteran populations (44.2% vs. 8.6% and 44.2% vs. 7.7%, respectively, both P < .00001). Among the 72 MIBH patients reporting cannabis use, 62 (86.1%) reported THC or combination product use, and 10 (13.9%) reported CBD product use. Concurrent medication use, including psychotropic medications use, did not differ significantly between cannabis users and nonusers. Conclusions Self-reported cannabis use is significantly higher in the MIBH population than in similarly aged individuals in the general population and significantly more frequent among younger than older members of this cohort. Self-reported reasons for cannabis use in this cohort included mTBI-associated neuropsychiatric symptoms, sleep disturbances, and pain for which standard treatments (both pharmacologic and nonpharmacologic) provided insufficient relief and/or produced treatment-limiting adverse events. However, cannabis use did not provide sufficient improvement in those symptoms to obviate the need for further evaluation and treatment of those problems at MIBH or to replace, in part or in whole, standard medications and other treatments for those problems. Further study of cannabis use, including standardized individual cannabinoid (i.e., THC and CBD) and whole-plant cannabis preparations, in this and similar cohorts is needed to more fully understand the drivers, benefits, risks, and safety of cannabis use in this and in similar Veteran populations, as well as the potential pharmacological and/or nonpharmacological therapeutic alternatives to cannabis use.

Higher Risk, Higher Reward? Self‐Reported Effects of Real‐World Cannabis Use in Parkinson's Disease

Article

Jan 2022

Background: Despite limited evidence, people with Parkinson's disease (PD) use cannabis for therapeutic purposes. Given barriers to performing randomized trials, exploring real-world experiences with cannabis in PD is valuable. Objective: Investigate the frequency and magnitude of symptomatic effects reported with cannabis use in PD. Methods: An anonymous, 15-question, web-based survey was deployed on Fox Insight. Cannabis product types were defined (by relative tetrahydrocannabinol [THC] and cannabidiol [CBD] content) and respondents were asked to reference product labels. Questions focused on use patterns and subjective effects on 36 predefined symptoms (rated -2-markedly worse to +2-markedly better). Results: 1,881 people with PD responded (58.5% men; mean age 66.5; 50.5% <3 years of PD). 73.0% of respondents reported medicinal use, though 30.8% did not inform their doctor. 86.7% knew their type of cannabis product: 54.6% took higher CBD, 30.2% higher THC, and 15.2% took similar amounts of THC and CBD products. Most common use was oral administration, once daily, for less than six months. Frequent improvements were reported for pain, anxiety, agitation, and sleep (>50% of respondents, mean magnitude 1.28-1.51). Dry mouth, dizziness, and cognitive changes were common adverse effects (20.9%-30.8%, mean -1.13 to -1.21). Higher THC users reported more frequent improvements in depression, anxiety, and tremor, and more frequent worsening in dry mouth and bradykinesia than other product types. Conclusions: Respondents with PD reported using more CBD products, via oral administration, with mild subjective benefits primarily for sleep, pain, and mood. Higher THC products may be higher risk/higher reward for PD-related symptoms.

Cannabidiol Interacts Antagonistically with Cisplatin and Additively with Mitoxantrone in Various Melanoma Cell Lines—An Isobolographic Analysis

Article

Jun 2022
INT J MOL SCI

The medical application of cannabidiol (CBD) has been gathering increasing attention in recent years. This non-psychotropic cannabis-derived compound possesses antiepileptic, antipsychotic, anti-inflammatory and anxiolytic properties. Recent studies report that it also exerts antineoplastic effects in multiple types of cancers, including melanoma. In this in vitro study we tried to reveal the anticancer properties of CBD in malignant melanoma cell lines (SK-MEL 28, A375, FM55P and FM55M2) administered alone, as well as in combination with mitoxantrone (MTX) or cisplatin (CDDP). The effects of CBD on the viability of melanoma cells were measured by the MTT assay; cytotoxicity was determined in the LDH test and proliferation in the BrdU test. Moreover, the safety of CBD was tested in human keratinocytes (HaCaT) in LDH and MTT tests. Results indicate that CBD reduces the viability and proliferation of melanoma-malignant cells and exerts additive interactions with MTX. Unfortunately, CBD produced antagonistic interaction when combined with CDDP. CBD does not cause significant cytotoxicity in HaCaT cell line. In conclusion, CBD may be considered as a part of melanoma multi-drug therapy when combined with MTX. A special attention should be paid to the combination of CBD with CDDP due to the antagonistic interaction observed in the studied malignant melanoma cell lines.

Clinical Management of Sleep and Sleep Disorders With Cannabis and Cannabinoids: Implications to Practicing Psychiatrists

Article

Full-text available

Dec 2021

Phytocannabinoid derivatives are among the several compounds found in the cannabis plant. The phytocannabinoid chemicals Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are mostly responsible for the drug's behavioural effects. Chronic cannabis administration has been shown to disrupt circadian rhythms and reduce the duration of the deepest phase (Stage N3) of non-rapid eye movement (NREM) sleep. Cannabidiol is thought to be responsible for the disruption of the circadian rhythm, while THC is thought to be accountable for the changes in sleep architecture. The quality of one's sleep has a significant impact on cannabis abstinence or relapse. As a result, the diminished sleep-promoting efficiency of cannabis in chronic users, as well as the resulting sleep difficulties once cannabis use is stopped, may sabotage attempts to quit and raise the risk of relapse. In individuals with obstructive sleep apnea (OSA) who do not complain about the treatment process known as continuous positive airway pressure (CPAP), cannabinoids are one of the treatments being considered. In this regard, preclinical investigations have demonstrated that combining the agent oleamide and THC aids in the stabilisation of respiration in all stages of sleep as well as the maintenance of autonomic stability during sleep. The synthetic THC dronabinol was found to lower the apnea-hypopnea index (AHI) in a clinical investigation and is regarded safe for the short-term treatment of OSA. Patients experiencing nightmares who had been diagnosed with posttraumatic stress disorder (PTSD) were given the synthetic endocannabinoid receptor agonist nabilone. When compared to a placebo, the chemical proved helpful in reducing the frequency of nightmares. It's worth noting that a single study that looked at the effects of CBD on REM behavior disorder (RBD) found that symptoms improved. Based on the available findings, cannabinoids can be utilised as an alternate treatment for various sleep disorders. However, additional research is needed to corroborate the conclusions of these investigations.

Effects of Cannabis in Parkinson’s Disease: A Systematic Review and Meta-Analysis

Article

Full-text available

Dec 2021

The legalization of cannabis in many countries has allowed many Parkinson’s disease (PD) patients to turn to cannabis as a treatment. As such there is a growing interest from the PD community to be properly guided by evidence regarding potential treatment benefits of cannabis. This systematic review and meta-analysis aims to compile the best available evidence to help guide patients and their family, clinicians and researchers make informed decisions. A systematic search of the literature was conducted in June 2021. Five randomized controlled studies and eighteen non-randomized studies investigated cannabis treatment in PD patients. No compelling evidence was found to recommend the use of cannabis in PD patients. However, a potential benefit was identified with respect to alleviation of PD related tremor, anxiety, pain, improvement of sleep quality and quality of life. Given the relative paucity of well-designed randomized studies, there is an identified need for further investigation, particularly in these areas.

Employing Aeroponic Systems for the Clonal Propagation of Cannabis

Article

Full-text available

Dec 2021
JoVE

The Use of Marijuana Derivatives in Primary Care: An Evidence-Based Approach to Cannabidiol

Article

Aug 2021
J Nurse Pract

Curtis Fowler

Changes in the legality of marijuana for medicinal use and the further legalization for recreational use have brought about renewed interest in the properties of the cannabis plant. Cannabidiol (CBD), a derivative of the cannabis plant, has emerged as a widely available panacea. The purpose of this review is to discuss the differences in the active ingredients of the cannabis plant as well as the mechanisms by which CBD may provide benefit. In addition, the evidence for pain management and anxiety are evaluated. Finally, safety, tolerability, and legal issues surrounding CBD are examined.

Placebo Effects of Edible Cannabis: Reported Intoxication Effects at a 30-Minute Delay

Article

Full-text available

Nov 2017

Previous research has demonstrated the ability of non-active smoked cannabis cigarettes to induce subjective effects of intoxication (i.e., placebo effect). No studies have been conduced to test whether edible forms of cannabis, which are associated with a significant delay in onset of effect, are able to induce a placebo effect. In the present study, 20 participants were told that they would receive an edible cannabis lollipop containing a high dose of tetrahydrocannabinol (THC), but were instead given a placebo control. Measures of intoxication and mood were taken at baseline, 30 minutes, and 60 minutes post-ingestion of the placebo lollipop. Results of four repeated-measures ANOVAs found significant and quadratic changes across time in cannabis (ARCI m-scale) intoxication (F(2,18) = 4.90, p = .01, η² = .22) and negative mood (F(2,18) = 3.99, p = .05, η² = .19). Changes in positive mood and the overall measure of general intoxication (ARCI) failed to reach significance. The present study provides preliminary evidence that a placebo effect can be induced with inert edible agents when participants are told that they are receiving active THC. This is the first known study to demonstrate an edible cannabis intoxication placebo effect.

Inverted U-Shaped Dose-Response Curve of the Anxiolytic Effect of Cannabidiol during Public Speaking in Real Life

Article

Full-text available

May 2017

The purpose of this study was to investigate whether the anxiolytic effect of cannabidiol (CBD) in humans follows the same pattern of an inverted U-shaped dose-effect curve observed in many animal studies. Sixty healthy subjects of both sexes aged between 18 and 35 years were randomly assigned to five groups that received placebo, clonazepam (1 mg), and CBD (100, 300, and 900 mg). The subjects were underwent a test of public speaking in a real situation (TPSRS) where each subject had to speak in front of a group formed by the remaining participants. Each subject completed the anxiety and sedation factors of the Visual Analog Mood Scale and had their blood pressure and heart rate recorded. These measures were obtained in five experimental sessions with 12 volunteers each. Each session had four steps at the following times (minutes) after administration of the drug/placebo, as time 0: -5 (baseline), 80 (pre-test), 153 (speech), and 216 (post-speech). Repeated-measures analyses of variance showed that the TPSRS increased the subjective measures of anxiety, heart rate, and blood pressure. Student-Newman-Keuls test comparisons among the groups in each phase showed significant attenuation in anxiety scores relative to the placebo group in the group treated with clonazepam during the speech phase, and in the clonazepam and CBD 300 mg groups in the post-speech phase. Clonazepam was more sedative than CBD 300 and 900 mg and induced a smaller increase in systolic and diastolic blood pressure than CBD 300 mg. The results confirmed that the acute administration of CBD induced anxiolytic effects with a dose-dependent inverted U-shaped curve in healthy subjects, since the subjective anxiety measures were reduced with CBD 300 mg, but not with CBD 100 and 900 mg, in the post-speech phase.

Cannabis sativa: The Plant of the Thousand and One Molecules

Article

Full-text available

Feb 2016

Cannabis sativa L. is an important herbaceous species originating from Central Asia, which has been used in folk medicine and as a source of textile fibre since the dawn of times. This fast-growing plant has recently seen a resurgence of interest because of its multi-purpose applications: it is indeed a treasure trove of phytochemicals and a rich source of both cellulosic and woody fibres. Equally highly interested in this plant are the pharmaceutical and construction sectors, since its metabolites show potent bioactivities on human health and its outer and inner stem tissues can be used to make bioplastics and concrete-like material, respectively. In this review, the rich spectrum of hemp phytochemicals is discussed by putting a special emphasis on molecules of industrial interest, including cannabinoids, terpenoids and phenolic compounds, and their biosynthetic routes. Cannabinoids represent the most studied group of compounds, mainly due to their wide range of pharmaceutical effects in humans, including psychotropic activities. The therapeutic and commercial interests of some terpenoids and phenolic compounds, and in particular stilbenoids and lignans, are also highlighted in view of the most recent literature data. Biotechnological avenues to enhance the production and bioactivity of hemp secondary metabolites are proposed by discussing the power of plant genetic engineering and tissue culture. In particular two systems are reviewed, i.e. cell suspension and hairy root cultures. Additionally, an entire section is devoted to hemp trichomes, in the light of their importance as phytochemical factories. Ultimately, prospects on the benefits linked to the use of the -omics technologies, such as metabolomics and transcriptomics to speed up the identification and the large-scale production of lead agents from bioengineered Cannabis cell culture, are presented.

A Runner’s high depends on cannabinoid receptors in mice

Article

Full-text available

Oct 2015

Exercise is rewarding, and long-distance runners have described a runner’s high as a sudden pleasant feeling of euphoria, anxiolysis, sedation, and analgesia. A popular belief has been that endogenous endorphins mediate these beneficial effects. However, running exercise increases blood levels of both β-endorphin (an opioid) and anandamide (an endocannabinoid). Using a combination of pharmacologic, molecular genetic, and behavioral studies in mice, we demonstrate that cannabinoid receptors mediate acute anxiolysis and analgesia after running. We show that anxiolysis depends on intact cannabinoid receptor 1 (CB1) receptors on forebrain GABAergic neurons and pain reduction on activation of peripheral CB1 and CB2 receptors. We thus demonstrate that the endocannabinoid system is crucial for two main aspects of a runner’s high. Sedation, in contrast, was not influenced by cannabinoid or opioid receptor blockage, and euphoria cannot be studied in mouse models.

Cannabidiol in Humans—The Quest for Therapeutic Targets

Article

Full-text available

Dec 2012

Cannabidiol (CBD), a major phytocannabinoid constituent of cannabis, is attracting growing attention in medicine for its anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties. However, up to this point, a comprehensive literature review of the effects of CBD in humans is lacking. The aim of the present systematic review is to examine the randomized and crossover studies that administered CBD to healthy controls and to clinical patients. A systematic search was performed in the electronic databases PubMed and EMBASE using the key word "cannabidiol". Both monotherapy and combination studies (e.g., CBD + ∆9-THC) were included. A total of 34 studies were identified: 16 of these were experimental studies, conducted in healthy subjects, and 18 were conducted in clinical populations, including multiple sclerosis (six studies), schizophrenia and bipolar mania (four studies), social anxiety disorder (two studies), neuropathic and cancer pain (two studies), cancer anorexia (one study), Huntington's disease (one study), insomnia (one study), and epilepsy (one study). Experimental studies indicate that a high-dose of inhaled/intravenous CBD is required to inhibit the effects of a lower dose of ∆9-THC. Moreover, some experimental and clinical studies suggest that oral/oromucosal CBD may prolong and/or intensify ∆9-THC-induced effects, whereas others suggest that it may inhibit ∆9-THC-induced effects. Finally, preliminary clinical trials suggest that high-dose oral CBD (150-600 mg/d) may exert a therapeutic effect for social anxiety disorder, insomnia and epilepsy, but also that it may cause mental sedation. Potential pharmacokinetic and pharmacodynamic explanations for these results are discussed.

Effects of ipsapirone and cannabidiol on human experimental anxiety

Article

Full-text available

Jan 1993
J PSYCHOPHARMACOL

The effects of ipsapirone and cannabidiol (CBD) on healthy volunteers submitted to a simulated public speaking (SPS) test were compared with those of the anxiolytic benzodiazepine diazepam and placebo. Four independent groups of 10 subjects received, under a double-blind design, placebo or one of the following drugs: CBD (300 mg), diazepam (10 mg) or ipsapirone (5 mg). Subjective anxiety was evaluated through the Visual Analogue Mood Scale (VAMS) and the State-trait Anxiety Inventory (STAI). The VAMS anxiety factor showed that ipsapirone attenuated SPS-induced anxiety while CBD decreased anxiety after the SPS test. Diazepam, on the other hand, was anxiolytic before and after the SPS test, but had no effect on the increase in anxiety induced by the speech test. Only ipsapirone attenuated the increase in systolic blood pressure induced by the test. Significant sedative effects were only observed with diazepam. The results suggest that ipsapirone and CBD have anxiolytic properties in human volunteers submitted to a stressful situation.

Prescribing cannabis for harm reduction

Article

Full-text available

Jan 2012

Mark Collen

Neuropathic pain affects between 5% and 10% of the US population and can be refractory to treatment. Opioids may be recommended as a second-line pharmacotherapy but have risks including overdose and death. Cannabis has been shown to be effective for treating nerve pain without the risk of fatal poisoning. The author suggests that physicians who treat neuropathic pain with opioids should evaluate their patients for a trial of cannabis and prescribe it when appropriate prior to using opioids. This harm reduction strategy may reduce the morbidity and mortality rates associated with prescription pain medications.

Cannabidiol Reduces the Anxiety Induced by Simulated Public Speaking in Treatment-Naive Social Phobia Patients

Article

Full-text available

Feb 2011
NEUROPSYCHOPHARMACOL

Generalized Social Anxiety Disorder (SAD) is one of the most common anxiety conditions with impairment in social life. Cannabidiol (CBD), one major non-psychotomimetic compound of the cannabis sativa plant, has shown anxiolytic effects both in humans and in animals. This preliminary study aimed to compare the effects of a simulation public speaking test (SPST) on healthy control (HC) patients and treatment-naïve SAD patients who received a single dose of CBD or placebo. A total of 24 never-treated patients with SAD were allocated to receive either CBD (600 mg; n=12) or placebo (placebo; n=12) in a double-blind randomized design 1 h and a half before the test. The same number of HC (n=12) performed the SPST without receiving any medication. Each volunteer participated in only one experimental session in a double-blind procedure. Subjective ratings on the Visual Analogue Mood Scale (VAMS) and Negative Self-Statement scale (SSPS-N) and physiological measures (blood pressure, heart rate, and skin conductance) were measured at six different time points during the SPST. The results were submitted to a repeated-measures analysis of variance. Pretreatment with CBD significantly reduced anxiety, cognitive impairment and discomfort in their speech performance, and significantly decreased alert in their anticipatory speech. The placebo group presented higher anxiety, cognitive impairment, discomfort, and alert levels when compared with the control group as assessed with the VAMS. The SSPS-N scores evidenced significant increases during the testing of placebo group that was almost abolished in the CBD group. No significant differences were observed between CBD and HC in SSPS-N scores or in the cognitive impairment, discomfort, and alert factors of VAMS. The increase in anxiety induced by the SPST on subjects with SAD was reduced with the use of CBD, resulting in a similar response as the HC.

Antianxiety effect of cannabidiol in the elevated plus-maze

Article

Full-text available

Feb 1990

In order to assess the presence of anxiolytic properties in cannabidiol (CBD) the drug was tested in an elevated plus-maze model of anxiety, in rats. Doses of 2.5, 5.0 and 10.0 mg/kg significantly increased the entry ratio (open/total number of entries), an anxiolytic-like effect. CBD at a dose of 20.0 mg/kg was no longer effective. None of the doses of CBD used changed total number of entries, a measure of total exploratory activity. Diazepam (2.0 mg/kg) also caused an anxiolytic-like effect in this model. These results indicate that CBD causes a selective anxiolytic effect in the elevated plus-maze, within a limited range of doses.

Effect of cannabidiol on plasma prolactin, growth hormone and cortisol in human volunteers

Article

Full-text available

Mar 1993
BRAZ J MED BIOL RES

In the present study, we investigated the effects of cannabidiol (CBD) on plasma prolactin, growth hormone and cortisol of 11 normal volunteers who received placebo or CBD at the doses of 300 mg (N = 7) or 600 mg (N = 4), po, in a double-blind manner during two experimental sessions separated by an interval of at least one week. The sessions were held in the morning and consisted of blood collection and application of self-evaluation scales before and after drug injection (-35 to 180 min). Hormonal measurements were performed by radioimmunoassay. Basal prolactin (11.5 +/- 4.3 ng/ml) and growth hormone (1.5 +/- 0.7 ng/ml) levels were unchanged after placebo and CBD. In contrast, plasma cortisol levels decreased significantly during the placebo sessions (basal measurement = 11.0 +/- 3.7 micrograms/dl; 120 min after placebo = 7.1 +/- 3.9 micrograms/dl), in agreement with the normal circadian rhythm of this hormone. This decrease in cortisol levels was significantly attenuated after CBD (basal measurement = 10.5 +/- 4.9 micrograms/dl; 120 min after 300 mg CBD = 9.9 +/- 6.2 micrograms/dl; 120 min after 600 mg CBD = 11.6 +/- 11.6 micrograms/dl). CBD was also found to have a sedative effect as determined by the self-evaluation scales. The present results suggest that CBD interferes with cortisol secretion.

Challenges towards Revitalizing Hemp: A Multifaceted Crop

Article

Sep 2017
TRENDS PLANT SCI

Hemp has been an important crop throughout human history for food, fiber, and medicine. Despite significant progress made by the international research community, the basic biology of hemp plants remains insufficiently understood. Clear objectives are needed to guide future research. As a semi-domesticated plant, hemp has many desirable traits that require improvement, including eliminating seed shattering, enhancing the quantity and quality of stem fiber, and increasing the accumulation of phytocannabinoids. Methods to manipulate the sex of hemp plants will also be important for optimizing yields of seed, fiber, and cannabinoids. Currently, research into trait improvement is hindered by the lack of molecular techniques adapted to hemp. Here we review how addressing these limitations will help advance our knowledge of plant biology and enable us to fully domesticate and maximize the agronomic potential of this promising crop.

An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies

Article

Jun 2017

Introduction: This literature survey aims to extend the comprehensive survey performed by Bergamaschi et al. in 2011 on cannabidiol (CBD) safety and side effects. Apart from updating the literature, this article focuses on clinical studies and CBD potential interactions with other drugs. Results: In general, the often described favorable safety profile of CBD in humans was confirmed and extended by the reviewed research. The majority of studies were performed for treatment of epilepsy and psychotic disorders. Here, the most commonly reported side effects were tiredness, diarrhea, and changes of appetite/weight. In comparison with other drugs, used for the treatment of these medical conditions, CBD has a better side effect profile. This could improve patients' compliance and adherence to treatment. CBD is often used as adjunct therapy. Therefore, more clinical research is warranted on CBD action on hepatic enzymes, drug transporters, and interactions with other drugs and to see if this mainly leads to positive or negative effects, for example, reducing the needed clobazam doses in epilepsy and therefore clobazam's side effects. Conclusion: This review also illustrates that some important toxicological parameters are yet to be studied, for example, if CBD has an effect on hormones. Additionally, more clinical trials with a greater number of participants and longer chronic CBD administration are still lacking.

Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome

Article

May 2017

Background The Dravet syndrome is a complex childhood epilepsy disorder that is associated with drug-resistant seizures and a high mortality rate. We studied cannabidiol for the treatment of drug-resistant seizures in the Dravet syndrome. Methods In this double-blind, placebo-controlled trial, we randomly assigned 120 children and young adults with the Dravet syndrome and drug-resistant seizures to receive either cannabidiol oral solution at a dose of 20 mg per kilogram of body weight per day or placebo, in addition to standard antiepileptic treatment. The primary end point was the change in convulsive-seizure frequency over a 14-week treatment period, as compared with a 4-week baseline period. Results The median frequency of convulsive seizures per month decreased from 12.4 to 5.9 with cannabidiol, as compared with a decrease from 14.9 to 14.1 with placebo (adjusted median difference between the cannabidiol group and the placebo group in change in seizure frequency, −22.8 percentage points; 95% confidence interval [CI], −41.1 to −5.4; P=0.01). The percentage of patients who had at least a 50% reduction in convulsive-seizure frequency was 43% with cannabidiol and 27% with placebo (odds ratio, 2.00; 95% CI, 0.93 to 4.30; P=0.08). The patient’s overall condition improved by at least one category on the seven-category Caregiver Global Impression of Change scale in 62% of the cannabidiol group as compared with 34% of the placebo group (P=0.02). The frequency of total seizures of all types was significantly reduced with cannabidiol (P=0.03), but there was no significant reduction in nonconvulsive seizures. The percentage of patients who became seizure-free was 5% with cannabidiol and 0% with placebo (P=0.08). Adverse events that occurred more frequently in the cannabidiol group than in the placebo group included diarrhea, vomiting, fatigue, pyrexia, somnolence, and abnormal results on liver-function tests. There were more withdrawals from the trial in the cannabidiol group. Conclusions Among patients with the Dravet syndrome, cannabidiol resulted in a greater reduction in convulsive-seizure frequency than placebo and was associated with higher rates of adverse events. (Funded by GW Pharmaceuticals; ClinicalTrials.gov number, NCT02091375.)

Beyond the CB1 Receptor: Is Cannabidiol the Answer for Disorders of Motivation?

Article

Feb 2016
ANNU REV NEUROSCI

The Cannabis sativa plant has been used to treat various physiological and psychiatric conditions for millennia. Current research is focused on isolating potentially therapeutic chemical constituents from the plant for use in the treatment of many central nervous system disorders. Of particular interest is the primary nonpsychoactive constituent cannabidiol (CBD). Unlike Δ9-tetrahydrocannabinol (THC), CBD does not act through the cannabinoid type 1 (CB1) receptor but has many other receptor targets that may play a role in psychiatric disorders. Here we review preclinical and clinical data outlining the therapeutic efficacy of CBD for the treatment of motivational disorders such as drug addiction, anxiety, and depression. Across studies, findings suggest promising treatment effects and potentially overlapping mechanisms of action for CBD in these disorders and indicate the need for further systematic investigation of the viability of CBD as a psychiatric pharmacotherapy. Expected final online publication date for the Annual Review of Neuroscience Volume 39 is July 08, 2016. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.

Comprehensive Review of Medicinal Marijuana, Cannabinoids, and Therapeutic Implications in Medicine and Headache: What a Long Strange Trip It's Been …

Article

May 2015

Eric P Baron

Background: The use of cannabis, or marijuana, for medicinal purposes is deeply rooted though history, dating back to ancient times. It once held a prominent position in the history of medicine, recommended by many eminent physicians for numerous diseases, particularly headache and migraine. Through the decades, this plant has taken a fascinating journey from a legal and frequently prescribed status to illegal, driven by political and social factors rather than by science. However, with an abundance of growing support for its multitude of medicinal uses, the misguided stigma of cannabis is fading, and there has been a dramatic push for legalizing medicinal cannabis and research. Almost half of the United States has now legalized medicinal cannabis, several states have legalized recreational use, and others have legalized cannabidiol-only use, which is one of many therapeutic cannabinoids extracted from cannabis. Physicians need to be educated on the history, pharmacology, clinical indications, and proper clinical use of cannabis, as patients will inevitably inquire about it for many diseases, including chronic pain and headache disorders for which there is some intriguing supportive evidence. Objective: To review the history of medicinal cannabis use, discuss the pharmacology and physiology of the endocannabinoid system and cannabis-derived cannabinoids, perform a comprehensive literature review of the clinical uses of medicinal cannabis and cannabinoids with a focus on migraine and other headache disorders, and outline general clinical practice guidelines. Conclusion: The literature suggests that the medicinal use of cannabis may have a therapeutic role for a multitude of diseases, particularly chronic pain disorders including headache. Supporting literature suggests a role for medicinal cannabis and cannabinoids in several types of headache disorders including migraine and cluster headache, although it is primarily limited to case based, anecdotal, or laboratory-based scientific research. Cannabis contains an extensive number of pharmacological and biochemical compounds, of which only a minority are understood, so many potential therapeutic uses likely remain undiscovered. Cannabinoids appear to modulate and interact at many pathways inherent to migraine, triptan mechanisms ofaction, and opiate pathways, suggesting potential synergistic or similar benefits. Modulation of the endocannabinoid system through agonism or antagonism of its receptors, targeting its metabolic pathways, or combining cannabinoids with other analgesics for synergistic effects, may provide the foundation for many new classes of medications. Despite the limited evidence and research suggesting a role for cannabis and cannabinoids in some headache disorders, randomized clinical trials are lacking and necessary for confirmation and further evaluation.

Cannabidiol: Pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders

Article

May 2014

To present a summary of current scientific evidence about the cannabinoid, cannabidiol (CBD) with regard to its relevance to epilepsy and other selected neuropsychiatric disorders. We summarize the presentations from a conference in which invited participants reviewed relevant aspects of the physiology, mechanisms of action, pharmacology, and data from studies with animal models and human subjects. Cannabis has been used to treat disease since ancient times. Δ9-Tetrahydrocannabinol (Δ9-THC) is the major psychoactive ingredient and CBD is the major nonpsychoactive ingredient in cannabis. Cannabis and Δ9-THC are anticonvulsant in most animal models but can be proconvulsant in some healthy animals. The psychotropic effects of Δ9-THC limit tolerability. CBD is anticonvulsant in many acute animal models, but there are limited data in chronic models. The antiepileptic mechanisms of CBD are not known, but may include effects on the equilibrative nucleoside transporter; the orphan G-protein-coupled receptor GPR55; the transient receptor potential of vanilloid type-1 channel; the 5-HT1a receptor; and the α3 and α1 glycine receptors. CBD has neuroprotective and antiinflammatory effects, and it appears to be well tolerated in humans, but small and methodologically limited studies of CBD in human epilepsy have been inconclusive. More recent anecdotal reports of high-ratio CBD:Δ9-THC medical marijuana have claimed efficacy, but studies were not controlled. CBD bears investigation in epilepsy and other neuropsychiatric disorders, including anxiety, schizophrenia, addiction, and neonatal hypoxic-ischemic encephalopathy. However, we lack data from well-powered double-blind randomized, controlled studies on the efficacy of pure CBD for any disorder. Initial dose-tolerability and double-blind randomized, controlled studies focusing on target intractable epilepsy populations such as patients with Dravet and Lennox-Gastaut syndromes are being planned. Trials in other treatment-resistant epilepsies may also be warranted.A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Blurred Boundaries: The Therapeutics and Politics of Medical Marijuana

Article

Feb 2012
MAYO CLIN PROC

J Michael Bostwick

For 5 millennia, Cannabis sativa has been used throughout the world medically, recreationally, and spiritually. From the mid-19th century to the 1930s, American physicians prescribed it for a plethora of indications, until the federal government started imposing restrictions on its use, culminating in 1970 with the US Congress classifying it as a Schedule I substance, illegal, and without medical value. Simultaneous with this prohibition, marijuana became the United States' most widely used illicit recreational drug, a substance generally regarded as pleasurable and relaxing without the addictive dangers of opioids or stimulants. Meanwhile, cannabis never lost its cachet in alternative medicine circles, going mainstream in 1995 when California became the first of 16 states to date to legalize its medical use, despite the federal ban. Little about cannabis is straightforward. Its main active ingredient, δ-9-tetrahydrocannabinol, was not isolated until 1964, and not until the 1990s were the far-reaching modulatory activities of the endocannabinoid system in the human body appreciated. This system's elucidation raises the possibility of many promising pharmaceutical applications, even as draconian federal restrictions that hamstring research show no signs of softening. Recreational use continues unabated, despite growing evidence of marijuana's addictive potential, particularly in the young, and its propensity for inducing and exacerbating psychotic illness in the susceptible. Public approval drives medical marijuana legalization efforts without the scientific data normally required to justify a new medication's introduction. This article explores each of these controversies, with the intent of educating physicians to decide for themselves whether marijuana is panacea, scourge, or both. PubMed searches were conducted using the following keywords: medical marijuana, medical cannabis, endocannabinoid system, CB1 receptors, CB2 receptors, THC, cannabidiol, nabilone, dronabinol, nabiximols, rimonabant, marijuana legislation, marijuana abuse, marijuana dependence, and marijuana and schizophrenia. Bibliographies were hand searched for additional references relevant to clarifying the relationships between medical and recreational marijuana use and abuse.

Antidepressant-like effects of cannabidiol in mice: Possible involvement of 5-HT 1A receptors

Article

Dec 2009
BRIT J PHARMACOL

Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa that induces anxiolytic- and antipsychotic-like effects in animal models. Effects of CBD may be mediated by the activation of 5-HT(1A) receptors. As 5-HT(1A) receptor activation may induce antidepressant-like effects, the aim of this work was to test the hypothesis that CBD would have antidepressant-like activity in mice as assessed by the forced swimming test. We also investigated if these responses depended on the activation of 5-HT(1A) receptors and on hippocampal expression of brain-derived neurotrophic factor (BDNF). Male Swiss mice were given (i.p.) CBD (3, 10, 30, 100 mg*kg(-1)), imipramine (30 mg*kg(-1)) or vehicle and were submitted to the forced swimming test or to an open field arena, 30 min later. An additional group received WAY100635 (0.1 mg*kg(-1), i.p.), a 5-HT(1A) receptor antagonist, before CBD (30 mg*kg(-1)) and assessment by the forced swimming test. BDNF protein levels were measured in the hippocampus of another group of mice treated with CBD (30 mg*kg(-1)) and submitted to the forced swimming test. CBD (30 mg*kg(-1)) treatment reduced immobility time in the forced swimming test, as did the prototype antidepressant imipramine, without changing exploratory behaviour in the open field arena. WAY100635 pretreatment blocked CBD-induced effect in the forced swimming test. CBD (30 mg*kg(-1)) treatment did not change hippocampal BDNF levels. CBD induces antidepressant-like effects comparable to those of imipramine. These effects of CBD were probably mediated by activation of 5-HT(1A) receptors.

Cannabis in painful HIV-associated sensory neuropathy

Article

Mar 2007
NEUROLOGY

To determine the effect of smoked cannabis on the neuropathic pain of HIV-associated sensory neuropathy and an experimental pain model. Prospective randomized placebo-controlled trial conducted in the inpatient General Clinical Research Center between May 2003 and May 2005 involving adults with painful HIV-associated sensory neuropathy. Patients were randomly assigned to smoke either cannabis (3.56% tetrahydrocannabinol) or identical placebo cigarettes with the cannabinoids extracted three times daily for 5 days. Primary outcome measures included ratings of chronic pain and the percentage achieving >30% reduction in pain intensity. Acute analgesic and anti-hyperalgesic effects of smoked cannabis were assessed using a cutaneous heat stimulation procedure and the heat/capsaicin sensitization model. Fifty patients completed the entire trial. Smoked cannabis reduced daily pain by 34% (median reduction; IQR = -71, -16) vs 17% (IQR = -29, 8) with placebo (p = 0.03). Greater than 30% reduction in pain was reported by 52% in the cannabis group and by 24% in the placebo group (p = 0.04). The first cannabis cigarette reduced chronic pain by a median of 72% vs 15% with placebo (p < 0.001). Cannabis reduced experimentally induced hyperalgesia to both brush and von Frey hair stimuli (p < or = 0.05) but appeared to have little effect on the painfulness of noxious heat stimulation. No serious adverse events were reported. Smoked cannabis was well tolerated and effectively relieved chronic neuropathic pain from HIV-associated sensory neuropathy. The findings are comparable to oral drugs used for chronic neuropathic pain.

ORIGINAL RESEARCH & CONTRIBUTIONS Cannabidiol in Anxiety and Sleep: A Large Case Series 10

Oct 2015
13105-13113

J Fuss
J Steinle
L Bindila

The Permanente Journal • https://doi.org/10.7812/TPP/18-041 ORIGINAL RESEARCH & CONTRIBUTIONS Cannabidiol in Anxiety and Sleep: A Large Case Series 10. Fuss J, Steinle J, Bindila L, et al. A runner's high depends on cannabinoid receptors in mice. Proc Natl Acad Sci U S A 2015 Oct 20;112(42):13105-8. DOI: https://doi. org/10.1073/pnas.1514996112.

Did the DEA just quietly approve CBD?

Jun 2018

T Mitchell

Mitchell T. Did the DEA just quietly approve CBD? [Internet]. 2018 Jun 2 [cited 2018

VA: Drug Enforcement Administration, Diversion Control Division

Jan 2017

Springfield

Springfield, VA: Drug Enforcement Administration, Diversion Control Division; 2017 [cited 2018

What marijuana legalization in Canada could mean for the United States

Apr 2017

K Steinmetz

Steinmetz K. What marijuana legalization in Canada could mean for the United States [Internet]. New York, NY: Time; 2017 Apr 6 [cited 2018 Aug 7]. Available from: http:// time.com/4728091/canada-legalizing-marijuana-united-states-weed-pot/.

ORIGINAL RESEARCH & CONTRIBUTIONS Cannabidiol in Anxiety and Sleep: A Large Case Series 10

Oct 2015
13105-13113

O Devinsky
J H Cross
L Laux

Devinsky O, Cross JH, Laux L, et al; Cannabidiol in Dravet Syndrome Study Group. Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. N Engl J Med 2017 May 25;376(21):2011-20. DOI: https://doi.org/10.1056/NEJMoa1611618. ORIGINAL RESEARCH & CONTRIBUTIONS Cannabidiol in Anxiety and Sleep: A Large Case Series 10. Fuss J, Steinle J, Bindila L, et al. A runner's high depends on cannabinoid receptors in mice. Proc Natl Acad Sci U S A 2015 Oct 20;112(42):13105-8. DOI: https://doi. org/10.1073/pnas.1514996112.

Cannabidiol in Anxiety and Sleep: A Large Case Series

Abstract

No full-text available

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