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Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: A preliminary report
Abstract and Figures
Animal and human studies indicate that cannabidiol (CBD), a major constituent of cannabis, has anxiolytic properties. However, no study to date has investigated the effects of this compound on human pathological anxiety and its underlying brain mechanisms. The aim of the present study was to investigate this in patients with generalized social anxiety disorder (SAD) using functional neuroimaging. Regional cerebral blood flow (rCBF) at rest was measured twice using (99m)Tc-ECD SPECT in 10 treatment-naïve patients with SAD. In the first session, subjects were given an oral dose of CBD (400 mg) or placebo, in a double-blind procedure. In the second session, the same procedure was performed using the drug that had not been administered in the previous session. Within-subject between-condition rCBF comparisons were performed using statistical parametric mapping. Relative to placebo, CBD was associated with significantly decreased subjective anxiety (p < 0.001), reduced ECD uptake in the left parahippocampal gyrus, hippocampus, and inferior temporal gyrus (p < 0.001, uncorrected), and increased ECD uptake in the right posterior cingulate gyrus (p < 0.001, uncorrected). These results suggest that CBD reduces anxiety in SAD and that this is related to its effects on activity in limbic and paralimbic brain areas.
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... Dessa forma, 10 estudos foram selecionados. A partir dessa seleção, outros 4 artigos que são encontrados no Pubmed e estão dentro do escopo da pesquisa, mas não foram encontrados na nossa busca, foram acrescentados pela especialista, são eles: Colizzi et al. (16); Crippa et al. (17,18) e Masataka et al. (19). As informações de cada artigo foram organizadas de maneira descritiva, constando dos seguintes dados: informações gerais (título, autor(es) e ano de publicação), objetivos, metodologia e avaliação dos estudos, informações sobre participantes (número de pacientes, placebo e grupo controle), informações sobre o composto utilizado (canabinoide de escolha, dosagem e posologia). ...
... O CBD parece mitigar os efeitos ansiogênicos do THC (26,28,35), a exemplo do que tem sido relatado com outros efeitos indesejados do THC (36,37). Os efeitos ansiolíticos do CBD parecem estar associados à modulação da atividade em regiões límbicas e paralímbicas do cérebro (18,21). Em relação aos efeitos dos canabinoides sobre o estado de ansiedade de indivíduos hígidos, os resultados são menos conclusivos. ...
Os transtornos de ansiedade estão entre as doenças psiquiátricas mais comuns na população. Os fármacos ansiolíticos convencionais não apresentam boa resposta terapêutica. Diversos estudos têm descrito que os compostos canabinoides apresentam propriedades ansiolíticas. Essa revisão de escopo tem o objetivo de avaliar a eficácia e segurança desses compostos no tratamento de transtornos de ansiedade. Foram incluídos 14 estudos clínicos publicados na língua inglesa até dezembro de 2022. O canabidiol (CBD) apresentou na maioria dos estudos efeito ansiolítico, cujo efeito parece envolver a modulação da atividade da amígdala e do córtex cingulado anterior e posterior. O Δ-9-tetrahidrocanabinol (THC) apresentou perfil modulador distinto a depender da dose. Apesar dos resultados promissores, foram observadas algumas lacunas no que se refere à presença de efeitos adversos decorrentes da exposição a esses agentes farmacológicos nos artigos avaliados. O presente estudo sugere que o uso de compostos canabinoides derivados ou não da Cannabis sativa pode causar diversos impactos no sistema nervoso, particularmente sobre os estados de ansiedade e de humor, podendo produzir efeitos tanto ansiolíticos quanto ansiogênicos, que dependem da substância (e.g. CBD, THC ou a combinação desses agentes), da dosagem, e dos sujeitos ou do desenho experimental do estudo.
... Being Medhya (memory enhancer) and Uttejaka (Stimulant) in nature helps to improve intellect [6,24] and alertness of mind respectively. [54] Clinical researches report effectiveness of constituents of Cannabis such as nabilone [36,55,56] and cannabidiol [53,54] for the management of both anxiety and depression simultaneously. [36] Quality of life Statistically significant improvement in FACT-G scale's parameters confirms the processed herbal form of Cannabis possess role in improving QOL in cancer patients by combating multiple symptoms, similarly like its extract. ...
... Being Medhya (memory enhancer) and Uttejaka (Stimulant) in nature helps to improve intellect [6,24] and alertness of mind respectively. [54] Clinical researches report effectiveness of constituents of Cannabis such as nabilone [36,55,56] and cannabidiol [53,54] for the management of both anxiety and depression simultaneously. [36] Quality of life Statistically significant improvement in FACT-G scale's parameters confirms the processed herbal form of Cannabis possess role in improving QOL in cancer patients by combating multiple symptoms, similarly like its extract. ...
Introduction: Pain is a common and complex symptom of cancer having physical, social, spiritual and psychological aspects. Approximately 70%–80% of cancer patients experiences pain, as reported in India. Ayurveda recommends use of Shodhita (Processed) Bhanga (Cannabis) for the management of pain but no research yet carried out on its clinical effectiveness. Objective: To assess the analgesic potential of JalaPrakshalana (Water-wash) processed Cannabis sativa L. leaves powder in cancer patients with deprived quality of life (QOL) through openlabel single arm clinical trial.
Materials and Methods: Waterwash processed Cannabis leaves powder filled in capsule, was administered in 24 cancer patients with deprived QOL presenting complaints of pain, anxiety or depression; for a period of 4 weeks; in a dose of 250 mg thrice a day; along with 50 ml of cow’s milk and 4 g of crystal sugar. Primary outcome i.e. pain was measured by Wong-Bakers FACES Pain Scale (FACES), Objective Pain Assessment (OPA) scale and Neuropathic Pain Scale (NPS). Secondary outcome namely anxiety was quantified by Hospital Anxiety and Depression Scale (HADS), QOL by FACT-G scale, performance score by Eastern Cooperative Oncology Group (ECOG) and Karnofsky score.
Results: Significant reduction in pain was found on FACES Pain Scale (P < 0.05), OPA (P < 0.05), NPS (P < 0.001), HADS (P < 0.001), FACT-G scale (P < 0.001), performance status score like ECOG (P < 0.05) and Karnofsky score (P < 0.01).
Conclusion: Jalaprakshalana Shodhita Bhanga powder in a dose of 250 mg thrice per day; relieves cancerinduced pain, anxiety and depression significantly and does not cause any major adverse effect and withdrawal symptoms during trial period
... A few studies researching other aspects (e.g., pain) have also reported mood changes as a secondary outcome (Table 5). For instance, the analgesic effects, safety, and tolerability of acute CBD administration (200,400, 800 mg/person; 2.9, 5.7, 11.4 mg/kg bw/day) has been investigated in healthy volunteers, whereby CBD had subtle, dose-dependent subjective effects on mood [56]. However, this study presented several limitations, such as the source and frequency of CBD administration being poorly described. ...
... None of these trials showed effects of CBD in the dose range < 300 mg/day (4.3 mg/kg bw/day) on anxiety (Table 6). By contrast, all included studies investigating higher doses of 300 mg CBD/day (4.3 mg/kg bw/day) [72,106,194,195,197,198], 350 mg CBD/day (5 mg/kg bw/day) [199], or 400 mg CBD/day (5.7 mg/kg bw/day [57,74,200] reported positive effects on anxiety. However, some of these studies were conducted in patients with social anxiety disorders [198] or heroin use disorders [74], which may not be directly transferrable to healthy subjects, e.g., consumers of food supplements. ...
Background: Cannabidiol (CBD) is a cannabinoid present in the hemp plant (Cannabis sativa L.). Non-medicinal CBD oils with typically 5–40% CBD are advertised for various alleged positive health effects. While such foodstuffs containing cannabinoids are covered by the Novel Food Regulation in the European Union (EU), none of these products have yet been authorized. Nevertheless, they continue to be available on the European market. Methods: The Permanent Senate Commission on Food Safety (SKLM) of the German Research Foundation (DFG) reviewed the currently available data on adverse and potential beneficial effects of CBD in the dose range relevant for foods. Results: Increased liver enzyme activities were observed in healthy volunteers following administration of 4.3 mg CBD/kg bw/day and higher for 3–4 weeks. As lower doses were not tested, a no observed adverse effect level (NOAEL) could not be derived, and the dose of 4.3 mg/kg bw/day was identified as the lowest observed adverse effect level (LOAEL). Based on the CBD content and dose recommendations of CBD products on the market, the SKLM considered several exposure scenarios and concluded that the LOAEL for liver toxicity may be easily reached, e.g., via consumption of 30 drops of an oil containing 20% CBD, or even exceeded. A critical evaluation of the available data on potential beneficial health effects of CBD in the dose range at or below the LOAEL of 4.3 mg/kg bw/day revealed no scientific evidence that would substantiate health claims, e.g., in relation to physical performance, the cardiovascular, immune, and nervous system, anxiety, relaxation, stress, sleep, pain, or menstrual health. Conclusions: The SKLM concluded that consumption of CBD-containing foods/food supplements may not provide substantiated health benefits and may even pose a health risk to consumers.
... M. Harris et al., 2019;L. S. Harris, 1976;Kraft et al., 2008;Liktor-Busa et al., 2021;Sofia et al., 1975;van de Donk et al., 2019) Anti-anxiety (Almeida et al., 2013;Blessing et al., 2015;Campos et al., 2013;Chaves et al., 2021;Crippa et al., 2011;de Oliveira Ribeiro et al., 2012;Fogaça et al., 2018;Gomes et al., 2011Gomes et al., , 2012Gomes et al., , 2013Moreira et al., 2006;R de Mello Schier et al., 2014;de Schier et al., 2012) Anticonvulsant (Hill et al., 2012;Johnson et al., 1975;Lazarini-Lopes et al., 2020;Leite et al., 1982;Shirazi-Zand et al., 2013;Sofia et al., 1976;Thompson et al., 2016;Vilela et al., 2017;Zhu et al., 2014) Anti-depressant (Abdel-Salam et al., 2013;Ahn et al., 2021;Chaves et al., 2021;de Morais et al., 2018;R de Mello Schier et al., 2014;Réus et al., 2011;Sales et al., 2019;Silote et al., 2019) Antifungal (Khan & Javaid, 2020;Pal et al., 2013;Wanas et al., 2016) Antihypertensive (Girgih et al., 2014;Kosersky, 1978) Anti-inflammatory (Costa et al., 2004;Downer, 2020;Formukong et al., 1988;Gallily et al., 2018;Nallathambi et al., 2017;Rajan et al., 2016;Ryz et al., 2017) Anti-melanogenesis (Kim et al., 2020 Anti-microbial (Ali et al., 2012;Chakraborty et al., 2018;Essien, 2011;Karas et al., 2020;Martinenghi et al., 2020;Muscarà et al., 2021;Palmieri et al., 2021;Pasquali et al., 2020;Sarmadyan et al., 2014;Tahsin et al., 2021) Anti-oxidant (M. Ahmed et al., 2019;Cantele et al., 2020;Casares et al., 2020;di Giacomo et al., 2020;Girgih et al., 2011;Kitrytė et al., 2018;Kornpointner et al., 2021;Moccia et al., 2020;Muscarà et al., 2021;Nafis et al., 2019;Palmieri et al., 2021;Rajan et al., 2016;Smeriglio et al., 2020;Teh et al., 2016;Yan et al., 2015) Antiproliferative (Caffarel et al., 2008;Moccia et al., 2020;Omer et al., 2020;Sainz-Cort et al., 2020;Wong, 2017) Antipyretic (Bilir et al., 2018;Gercek et al., 2020;Morris et al., 2021) Anti-tumor (Baram et al., 2019;Grijo et al., 2019;Jaafari et al., 2007;Ligresti et al., 2006;Massi et al., 2004;McAllister et al., 2015;Todorova et al., 2021) Anxiolytic (Almeida et al., 2013;Crippa et al., 2011;Guimarães et al., 1994;Masataka, 2019;Moreira et al., 2006;R de Mello Schier et al., 2014;Schier et al., 2012) Cytotoxic (Nallathambi et al., 2018;Namdar et al., 2019;Sainz-Cort et al., 2020;Scott et al., 2015;Zengin et al., 2018) Neurodegenerative disease (Abdel-Salam et al., 2015;Amin & Ali, 2019;Cassano et al., 2020;di Giacomo et al., 2020;dos Reis Rosa Franco et al., 2021;Fernández-Ruiz et al., 2013;Iuvone et al., 2009;Mahdi et al., 2021;Milano et al., 2017;Rodriguez-Martin et al., 2019;Scotter et al., 2010;Watt & Karl, 2017) Sedative (de Souza Crippa et al., 2004;Nicholson et al., 2004;Pickens, 1981) ...
... S. Harris, 1976;Kraft et al., 2008;Liktor-Busa et al., 2021;Sofia et al., 1975;van de Donk et al., 2019) Anti-anxiety (Almeida et al., 2013;Blessing et al., 2015;Campos et al., 2013;Chaves et al., 2021;Crippa et al., 2011;de Oliveira Ribeiro et al., 2012;Fogaça et al., 2018;Gomes et al., 2011Gomes et al., , 2012Gomes et al., , 2013Moreira et al., 2006;R de Mello Schier et al., 2014;de Schier et al., 2012) Anticonvulsant (Hill et al., 2012;Johnson et al., 1975;Lazarini-Lopes et al., 2020;Leite et al., 1982;Shirazi-Zand et al., 2013;Sofia et al., 1976;Thompson et al., 2016;Vilela et al., 2017;Zhu et al., 2014) Anti-depressant (Abdel-Salam et al., 2013;Ahn et al., 2021;Chaves et al., 2021;de Morais et al., 2018;R de Mello Schier et al., 2014;Réus et al., 2011;Sales et al., 2019;Silote et al., 2019) Antifungal (Khan & Javaid, 2020;Pal et al., 2013;Wanas et al., 2016) Antihypertensive (Girgih et al., 2014;Kosersky, 1978) Anti-inflammatory (Costa et al., 2004;Downer, 2020;Formukong et al., 1988;Gallily et al., 2018;Nallathambi et al., 2017;Rajan et al., 2016;Ryz et al., 2017) Anti-melanogenesis (Kim et al., 2020 Anti-microbial (Ali et al., 2012;Chakraborty et al., 2018;Essien, 2011;Karas et al., 2020;Martinenghi et al., 2020;Muscarà et al., 2021;Palmieri et al., 2021;Pasquali et al., 2020;Sarmadyan et al., 2014;Tahsin et al., 2021) Anti-oxidant (M. Ahmed et al., 2019;Cantele et al., 2020;Casares et al., 2020;di Giacomo et al., 2020;Girgih et al., 2011;Kitrytė et al., 2018;Kornpointner et al., 2021;Moccia et al., 2020;Muscarà et al., 2021;Nafis et al., 2019;Palmieri et al., 2021;Rajan et al., 2016;Smeriglio et al., 2020;Teh et al., 2016;Yan et al., 2015) Antiproliferative (Caffarel et al., 2008;Moccia et al., 2020;Omer et al., 2020;Sainz-Cort et al., 2020;Wong, 2017) Antipyretic (Bilir et al., 2018;Gercek et al., 2020;Morris et al., 2021) Anti-tumor (Baram et al., 2019;Grijo et al., 2019;Jaafari et al., 2007;Ligresti et al., 2006;Massi et al., 2004;McAllister et al., 2015;Todorova et al., 2021) Anxiolytic (Almeida et al., 2013;Crippa et al., 2011;Guimarães et al., 1994;Masataka, 2019;Moreira et al., 2006;R de Mello Schier et al., 2014;Schier et al., 2012) Cytotoxic (Nallathambi et al., 2018;Namdar et al., 2019;Sainz-Cort et al., 2020;Scott et al., 2015;Zengin et al., 2018) Neurodegenerative disease (Abdel-Salam et al., 2015;Amin & Ali, 2019;Cassano et al., 2020;di Giacomo et al., 2020;dos Reis Rosa Franco et al., 2021;Fernández-Ruiz et al., 2013;Iuvone et al., 2009;Mahdi et al., 2021;Milano et al., 2017;Rodriguez-Martin et al., 2019;Scotter et al., 2010;Watt & Karl, 2017) Sedative (de Souza Crippa et al., 2004;Nicholson et al., 2004;Pickens, 1981) ...
... Major targeted brain structures include the hippocampus, prefrontal cortex, mesolimbic system, amygdala, caudate, substantia nigra, and hypothalamus (Crippa et al. 2004(Crippa et al. , 2010Castillo et al. 2010;Batalla et al. 2020;Lawn et al. 2020). ...
Cannabidiol (CBD) is a compound found in Cannabis sativa that is known for its neuroprotective, anti-inflammatory, analgesic, and anxiolytic properties. These properties make it a promising treatment for various neurological conditions. This study aimed to examine the effects of CBD on hypothalamic neurons at the transcriptome level using the adult-derived mHypoA-2/12 mouse cell line. The cells were exposed to four different CBD concentrations (ranging from 0.325 to 3 µM) for 6 and 24 h. Apart from the transcriptome analysis, apoptosis (caspase 3/7 activity) and viability (MTT) assays were performed. The obtained results showed that CBD enhanced cell viability, especially after 24 h of treatment and at lower or intermediate concentrations, and reduced apoptosis, with significant effects at the highest concentration. CBD caused moderate transcriptome profile changes (13 to 69 genes per treatment), with more genes affected at higher concentrations and shorter exposure times, indicating a stronger initial cellular response. Further analysis revealed that CBD affects several biological processes, including: intrinsic apoptosis suppression via p53 modulation, impacting genes like Bbc3 , Mdm2 , Cdkn1a , and Smad3 . Additionally, CBD influenced genes involved in extracellular matrix organization, including metalloproteinases ( Mmp-3 , Mmp-13 ) and their inhibitors ( Timp1 ), as well as collagen components ( Col11a1 ) and mitochondrial respiratory chain complexes ( mt-Nd5 , mt-Nd4 ). Genes related to serotonin and dopamine biosynthesis, as well as Aldh2 , were also impacted, linking CBD’s effects in hypothalamic neurons to potential benefits in managing alcohol use disorders. These findings suggest the hypothalamus is a significant target for CBD, warranting further investigation.
... Cannabis has emerged as a promising treatment alternative for fibromyalgia, supported by many studies examining its effectiveness in managing various symptoms associated with the condition [128][129][130]135]. The anti-inflammatory and anxiolytic properties of CBD, in conjunction with the analgesic and muscle-relaxant properties of THC, might yield a synergistic effect in addressing the multifaceted symptoms inherent to this disorder [136,137]. ...
Fibromyalgia is a chronic disease marked by extensive musculoskeletal pain, persistent fatigue, and cognitive impairments. Despite its high prevalence, the underlying pathological mechanisms of fibromyalgia are still not fully elucidated. Emerging research has identified the endocannabinoid system as an essential factor in modulating pain and other symptoms related to fibromyalgia. The endocannabinoid system plays a key role in many physiological processes such as pain perception, mood regulation, and inflammation. This review provides a powerful analysis of the principal aspects of fibromyalgia and examines the evidence regarding the involvement of the endocannabinoid system in this condition, focusing on its influence on pain modulation. Moreover, the dysregulation of the endocannabinoid system in fibromyalgia patients will be examined, with an assessment of how variations in endocannabinoid levels and receptor activity may contribute to the clinical manifestations of the condition. A better knowledge of this physiological system could lead to the development of novel strategies for managing fibromyalgia.
... As more cannabinoids are understood, the potential for market options may become more available (ElSohly & Gul, 2014). The interest in cannabinoids for medical use and aliment mitigation has been a focus for many decades and across areas (Clark et al., 1981;Crippa et al., 2011;Mandolini et al., 2018). The recent legislation in the United States caused increased hemp production and new and rapidly growing interest from various sectors (Hemp Business Journal, 2018;Nichols, 2018). ...
Following the 2018 Farm Bill, many US states allowed for hundreds of industrial hemp licenses, and the resulting production flooded markets. Floral industrial hemp (Cannabis sativa L.) offered prospects in essential oils for medicinal, flavoring, and fragrance additives. One major limitation for growers is the expense of Δ9‐tetrahydrocannabinol (Δ9THC) monitoring to meet legal compliance while maximizing cannabidiol (CBD) or cannabigerol (CBG) concentration for financial return. Cannabinoid analysis is not widely available, and shipping samples is legally challenging with state‐by‐state legislation. The study objectives were to evaluate whether near‐infrared spectroscopy (NIRS) could be used to rapidly and inexpensively quantify commonly produced hemp cannabinoid concentrations compared to industry standard high‐performance liquid chromatography (HPLC). A total of 448 tissue samples from 3 years of outdoor hemp cultivar, irrigation, and fertility trials were evaluated. Samples were dried and ground, and Δ8‐tetrahydrocannabinol (Δ8THC), Δ9THCD, tetrahydrocannabinolic acid (THCA), CBD, CBG, cannabichromene (CBC), cannabinol (CBN), cannabidivarin (CBDV), cannabidiol acid (CBDA), and cannabigerol acid (CBGA) were determined by HPLC with a diode array detector as reference measurements, prior to analysis by NIRS. Calibration equations were developed to assess whether NIRS can estimate cannabinoid concentrations. The three cannabinoids of most importance for floral hemp production (THCA, CBDA, and CBD) had the widest range in concentrations and the best correlation (R² = 0.71–0.87) between NIRS and HPLC, while other cannabinoids had limited concentration ranges and poorer correlation. The THC and CBD results are highly encouraging and indicate that NIRS is a robust tool for rapid and inexpensive quantification.
... In healthy humans and in patients with generalized social anxiety disorder, oral CBD reduced self-report measures of anxiety at baseline and during the Simulated Public Speaking Test (Bergamaschi et al. 2011;J. A. Crippa et al. 2004; J. A. S. Crippa et al. 2011;A. W. Zuardi et al. 1993). ...
Rationale
Clinical literature indicates there may be a therapeutic use of cannabidiol (CBD) for stress-related disorders. Preclinical literature remains conflicted regarding the underlying neurobehavioral mechanisms, reporting mixed effects of CBD (increased, decreased, or no effect) on anxiety- and fear-related behaviors. Preclinical data demonstrated that CBD modulates hypothalamus–pituitary–adrenal (HPA) axis gene expression; it is unknown whether CBD changes HPA axis responsivity and how this relates to altered behavior.
Objectives
We aimed to evaluate whether acute or chronic CBD administration would alter physiological and behavioral measures of HPA axis responsivity in male or female mice.
Methods
C57BL/6 mice of both sexes were injected with vehicle or CBD (30 mg/kg, i.p.) daily for 26 days. Plasma corticosterone (CORT) levels were evaluated following dexamethasone suppression and adrenocorticotropin hormone stimulation tests after acute and chronic CBD exposure. After chronic CBD, mice were tested for anxiety-like behavior using an elevated plus maze (EPM) and associative fear learning and memory using a trace fear conditioning (FC) protocol.
Results
Compared to vehicle, CBD induced a state of HPA axis hyperactivation, an effect which was significant in males; it also normalized anxiety-like behavior in female mice classified as having HPA axis hypofunction and primed all female mice for enhanced conditioned responding. Significant sex differences were also detected: females had greater plasma CORT levels and HPA axis responsivity than males, exhibited less EPM anxiety-like behavior, and were more responsive during FC.
Conclusions
CBD potentiated physiological and behavioral markers of HPA axis function and normalized anxiety-like behavior in a sex-specific manner. This observation has implications for cannabinoid-based drug development targeting individuals with stress-related disorders involving HPA axis hypofunction pathology.
... Not surprisingly, there is significant interest in pursuing the development of cannabinoid-based products for anxiety, particularly those rich in CBD. While additional work is needed, acute administration studies and clinical trials thus far have reported that CBD appears to be effective for reducing situational anxiety, such as public speaking tasks [45,46], and for reducing anxiety in those with moderate-to-severe anxiety [47], social anxiety disorder [48,49], and treatment-resistant anxiety [50]. In addition, a recent systematic review and meta-analysis [44] assessed eight clinical studies evaluating anxiety symptoms (i.e., anxiety disorders or anxiety induced by other medical conditions such as high paranoia and PTSD) in 316 participants (157 assigned to CBD treatment and 159 to a control group). ...
The relationship between cannabis use and mental health is complex, as studies often report seemingly contradictory findings regarding whether cannabis use results in more positive or negative treatment outcomes. With an increasing number of individuals using cannabis for both recreational (i.e., non-medical) and medical purposes, it is critical to gain a deeper understanding of the ways in which cannabis may be helpful or harmful for those diagnosed with psychiatric disorders. Although cannabis is composed of hundreds of compounds, studies assessing the effects of “cannabis” most often report the impact of delta-9-tetrahydrocannabinol (d9-THC), the primary intoxicating constituent of the plant. While d9-THC has documented therapeutic properties, negative clinical outcomes commonly associated with cannabis are generally related to d9-THC exposure. In contrast, non-intoxicating cannabinoids such as cannabidiol (CBD) show promise as potential treatment options for psychiatric symptoms. In this article, findings from studies and reviews examining the relationship between mental health conditions (mood, anxiety, psychosis, and post-traumatic stress disorder [PTSD]) and cannabis use are summarized to highlight critical variables that are often overlooked, including those associated with cannabis use patterns (e.g., frequency of use, amount used, cannabinoid exposure, product choice, and route of administration). Further, this article explores individual factors (e.g., age, sex, genetics/family history) that likely impact cannabis-related outcomes. Research to date suggests that youth and those with a family history or genetic liability for psychiatric disorders are at higher risk for negative outcomes, while more research is needed to fully understand unique effects related to sex and older age.
In-vivo neuroimaging allows the investigation of brain circuits involved in the experience of anxiety and of receptor changes associated with anxiety disorders. This review focuses on studies by research groups who have compared brain activation maps in different forms of anxiety and on binding studies of the benzodiazepine-GABA(A) receptor. Activation studies have revealed the involvement of many brain areas depending on the condition and the paradigm. However, the orbitofrontal cortex/anterior insula and the anterior cingulate are implicated in all the studies and may represent the nodal point between somatic and. cognitive symptoms of any form of anxiety. Most studies of binding at the benzodiazepine-GABA(A) receptor are not interpretable because of substantial methodological problems, however, regional and/or global reductions are the most consistent finding in panic disorder.
1. Despite increased understanding of the prevalence and pharmacotherapy of social phobia (or social anxiety disorder), the neurobiology of the disorder is little understood. 2. Little data exists on the effect of pharmacotherapeutic intervention on regional cerebral blood flow (rCBF) in this disorder. Patients (n=15) who met DSM-IV diagnostic criteria for social phobia were subjected to single photon emission computed tomography (SPECT) with technetium-99m hexamethylpropylene amine oxime (Tc-99m HMPAO) before and after an eight-week trial of pharmacotherapy with the selective serotonin reuptake inhibitor (SSRI) citalopram. 3. Pharmacotherapy led to significantly reduced activity in the anterior and lateral part of the left temporal cortex; the anterior, lateral and posterior part of the left mid frontal cortex; and the left cingulum. 4. Despite the small sample size, medication non-responders (n=6) had higher activity at baseline in the anterior and lateral part of the left temporal cortex and the lateral part of the left mid frontal regions compared with responders (n=9). These data from this exploratory study are consistent with work suggesting that the anxiety disorders share certain mediating neurocircuitry, although activity in other brain regions may differ. 5. Further research is necessary to determine the neurobiological underpinnings of social phobia.