Medicinal cannabis for psychiatric disorders: a clinically-focused systematic review
Jerome Sarris, Justin Sinclair, Diana Karamacoska, Maggie Davidson and Joseph Firth
BMC Psychiatry, 2020, 20, 24, 1-14.
Doi : 10.1186/s12888-019-2409-8
Background : Medicinal cannabis has received increased research attention over recent years due to loosening global regulatory changes. Medicinal cannabis has been reported to have potential efficacy in reducing pain, muscle spasticity, chemotherapy-induced nausea and vomiting, and intractable childhood epilepsy. Yet its potential application in the field of psychiatry is lesser known.
Methods : The first clinically-focused systematic review on the emerging medical application of cannabis across all major psychiatric disorders was conducted. Current evidence regarding whole plant formulations and plant-derived cannabinoid isolates in mood, anxiety, sleep, psychotic disorders and attention deficit/hyperactivity disorder (ADHD) is discussed; while also detailing clinical prescription considerations (including pharmacogenomics), occupational and public health elements, and future research recommendations. The systematic review of the literature was conducted during 2019, assessing the data from all case studies and clinical trials involving medicinal cannabis or plant-derived isolates for all major psychiatric disorders (neurological conditions and pain were omitted).
Results : The present evidence in the emerging field of cannabinoid therapeutics in psychiatry is nascent, and thereby it is currently premature to recommend cannabinoid-based interventions. Isolated positive studies have, however, revealed tentative support for cannabinoids (namely cannabidiol; CBD) for reducing social anxiety; with mixed (mainly positive) evidence for adjunctive use in schizophrenia. Case studies suggest that medicinal cannabis may be beneficial for improving sleep and post-traumatic stress disorder, however evidence is currently weak. Preliminary research findings indicate no benefit for depression from high delta-9 tetrahydrocannabinol (THC) therapeutics, or for CBD in mania. One isolated study indicates some potential efficacy for an oral cannabinoid/ terpene combination in ADHD. Clinical prescriptive consideration involves caution in the use of high-THC formulations (avoidance in youth, and in people with anxiety or psychotic disorders), gradual titration, regular assessment, and caution in cardiovascular and respiratory disorders, pregnancy and breast-feeding.
Conclusions : There is currently encouraging, albeit embryonic, evidence for medicinal cannabis in the treatment of a range of psychiatric disorders. Supportive findings are emerging for some key isolates, however, clinicians need to be mindful of a range of prescriptive and occupational safety considerations, especially if initiating higher dose THC formulas.
Keywords : Cannabinoids, Cannabidiol, Marijuana, Cannabis, CBD, THC, Pharmacogenomics, Medicinal plants, Mental health
The Cannabaceae family is a comparatively small family of flowering plants encompassing 11 genera and approximately 170 different species, a small number of which elicit a range of varying psychoactive effects . Several medical applications have been studied over the past decades, with the National Academies of Sciences, Engineering and Medicine (NASEM) recently holding the position that cannabis and cannabinoids demonstrate conclusive or substantial evidence for chronic pain in adults, chemo-therapy-induced nausea and vomiting and spasticity in multiple sclerosis, with limited evidence for use in increasing appetite in HIV/AIDS patients and improving symptoms of post-traumatic stress disorder (PTSD) .
While there is increasing psychiatric interest (and debate) regarding the potential mental health applications (in concert with concerns over the potential for triggering latent psychosis), historical evidence for the use of cannabis in mental health conditions is remarkably ancient. For instance, the Shen-nung Pen-tsao Ching (Divine Husbandman’s Materia Medica) described its benefit as an anti senility agent [3, 4], while in the Assyrian culture, cannabis was indicated as a drug for grief and sorrow [5, 6]. Sections of the Indian Atharva Veda (1500 BCE) suggest bhanga (Cannabis) exerted anxiolytic effects [5, 7], while in 1563, Da Orta  described cannabis as allaying anxiety and engendering laughter. With respect to modern use, contemporary consumers of cannabis report (as assessed via meta-analysis of patient usage data) that pain (64%), anxiety (50%), and depression/ mood (34%) are the most common reasons .
Increasing scientific research, conducted over recent years, has seen the regulatory pendulum swinging away from the United Nations Single Convention on Narcotic Drugs in 1961 (which recommends enforcement of cannabis use as illegal) , towards consideration of its potential use in medical conditions. Recent scientific evidence ascribes anxiolytic, neuroprotective, anti-oxidant, anti-inflammatory, anti-depressant, anti-psychotic and hypnotic pharmacological actions due to several phytochemicals commonly found in the cannabis genus [11, 12].
While Δ9-tetrahydrocannabinol (THC) is considered the main psychoactive constituent, other cannabinoids have also revealed less potent psychotropic effects. These include cannabidiol (CBD) , Δ8-tetrahydrocannabinol , and other less-studied cannabinoids including cannabinol (CBN) and Δ8 tetrahydrocannabivarin (THCV) . Further, many other constituents such as the terpenes (i.e. volatile organic compounds found mainly as essential oils in many plants), also provoke a range of biological effects, and produce the characteristic aroma of the plant . The hundreds of cannabis chemovars or varieties (commonly referred to as strains) developed over millennia have unique and complex constituent profiles, of which each may provide targeted therapeutic usage due to the unique synergistic combination of plant chemicals. Some pharmaceutical preparations have attempted to isolate the key constituents (there are over 140 phytocannabinoids ) to provide standardised formulas that may harness this ‘entourage effect’ [16, 18], while being able to provide batch-to-batch assurance of the medicine.
While other reviews have covered cannabis’ use in a range of conditions (cf. Whiting et al. 2015  for a general review of evidence for medicinal cannabis), none to date have provided both a systematic and ‘clinicallyfocused’ review on psychiatric disorders. As the focus was on emerging data for the use of mental health disorders, we omitted addiction and neurological disorders, which have been extensively covered elsewhere [10, 19], cf. pain [20–22], cf. epilepsy [23, 24], cf. movement disorders . A further motive for this paper focusing solely on psychiatric disorders, concerns cannabis users noting that self reported anxiety, insomnia, and depression symptoms are amongst the most common reasons for usage .
Thus, the primary purpose of this paper is to provide a systematic review of the current state of evidence in the emerging field of cannabinoid therapies for psychiatric disorders (PTSD, generalised anxiety disorder, social anxiety, insomnia, psychotic disorders, and attention-deficit hyperactivity disorder: ADHD). In addition, this review provides clinical prescriptive guidelines and consideration of both safety and occupational public health issues. We also provide discussion on considerations for future research in the field. Our intention was to provide a review of the extant literature to inform a discussion with clinical context and appropriate recommendations.
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