Cannabis, a cause for anxiety? A critical appraisal of the anxiogenic and anxiolytic properties

Abstract

Background Cannabis has been documented for use in alleviating anxiety. However, certain research has also shown that it can produce feelings of anxiety, panic, paranoia and psychosis. In humans, Δ9-tetrahydrocannabinol (THC) has been associated with an anxiogenic response, while anxiolytic activity has been attributed mainly to cannabidiol (CBD). In animal studies, the effects of THC are highly dose-dependent, and biphasic effects of cannabinoids on anxiety-related responses have been extensively documented. A more precise assessment is required of both the anxiolytic and anxiogenic potentials of phytocannabinoids, with an aim towards the development of the ‘holy grail’ in cannabis research, a medicinally-active formulation which may assist in the treatment of anxiety or mood disorders without eliciting any anxiogenic effects. Objectives To systematically review studies assessing cannabinoid interventions (e.g. THC or CBD or whole cannabis interventions) both in animals and humans, as well as recent epidemiological studies reporting on anxiolytic or anxiogenic effects from cannabis consumption. Method The articles selected for this review were identified up to January 2020 through searches in the electronic databases OVID MEDLINE, Cochrane Central Register of Controlled Trials, PubMed, and PsycINFO. Results Acute doses of CBD were found to reduce anxiety both in animals and humans, without having an anxiogenic effect at higher doses. Epidemiological studies tend to support an anxiolytic effect from the consumption of either CBD or THC, as well as whole plant cannabis. Conversely, the available human clinical studies demonstrate a common anxiogenic response to THC (especially at higher doses). Conclusion Based on current data, cannabinoid therapies (containing primarily CBD) may provide a more suitable treatment for people with pre-existing anxiety or as a potential adjunctive role in managing anxiety or stress-related disorders. However, further research is needed to explore other cannabinoids and phytochemical constituents present in cannabis (e.g. terpenes) as anxiolytic interventions. Future clinical trials involving patients with anxiety disorders are warranted due to the small number of available human studies.

Self-Reported Effects of Cannabis on ADHD Symptoms, ADHD Medication Side Effects, and ADHD-Related Executive Dysfunction

“…The majority of cannabis users taking ADHD medication reported that cannabis is beneficial for managing many of the side effects associated with ADHD medication, including stomach ache, headache, loss of appetite, sleeping problems, rebound, moodiness/irritability, and anxiety. While these findings are entirely novel, these self-reports are consistent with previous research demonstrating that acute cannabis use diminishes headache severity (Cuttler et al, 2020), improves appetite (Bonn-Miller et al, 2014), insomnia and sleep related problems (Choi et al, 2020; Cranford et al, 2017; Doremus et al, 2019), irritability (LaFrance et al, 2020), and anxiety (Cuttler et al, 2018; Sharpe et al, 2020) in the broader population. These symptoms represent many of the undesirable side effects that stimulant medications are known to cause and that can contribute to low adherence rates (Berman et al, 2009; Man et al, 2017; Zetterqvist et al, 2013).…”

Acute objective and subjective intoxication effects of legal-market high potency THC-dominant versus CBD-dominant cannabis concentrates

“…In contrast, individuals in the THC-dominant concentrate group did not report significant changes in anxiety or tension immediately post-use, but a significant reduction in anxiety from baseline did emerge at one-hour post-use. This is notable as human studies generally show an anxiogenic acute effect of THC, especially in high concentrations 50 .…”

“…However, some subjective data do show a preference for THC or whole cannabis products in the context of self-medicating for affect issues, with few reports of undesirable effects 50 , 51 . Furthermore, anxiogenic effects induced by more typically seen in individuals who fall into the category of infrequent or non-users, rather than those who use cannabis or THC products on a more regular basis 25 , 50 . Importantly, anxiety and tension levels were low overall in the study and do not reflect clinical levels of negative affect.…”

Prevalence and self-reported reasons of cannabis use for medical purposes in USA and Canada

“…Our finding was consistent with an online survey of medical cannabis users registered with a Canadian licensed producer, which found that anxiety was the most common mental health condition that cannabis was prescribed to treat (Turna et al 2019). This could be a reflection of the anxiolytic properties of cannabinoids, especially the use of CBD, which is suggested as an adjunctive treatment for anxiety or stress-related disorders (Sharpe et al 2020). The possible anxiolytic effects of CBD and other cannabinoids are demonstrated to mediate anxiety, stress, and restlessness in several animal and human studies (Crippa et al 2009;Fraguas-Sánchez & Torres-Suárez, 2018).…”