cbd and schizophrenia

In addition to the potential therapeutic effects of CBD for schizophrenia, CBD may also have a role in preventing or treating the psychosis related to recreational use of cannabis in vulnerable individuals. Cannabis continues to be the most commonly used illicit drug in the US, and with the spreading legalization for medical and recreational purposes, a lower proportion of people perceive the risk associated with regular cannabis use. At the same time, there is a decreasing ratio of CBD-to-THC in street cannabis from 1:14 in 1995 to 1:80 in 2014. Low CBD content may affect the overall impact of frequent cannabis use on mental health, which may become evident in the future. When discussing the medicinal use of cannabis, it is important to distinguish CBD, with its potential beneficial effects, from THC, with its controversial adverse effects, especially on individuals with psychotic disorders.

Dr Bassir Nia is Assistant Professor of Psychiatry, Yale University School of Medicine, New Haven, CT. Dr Bassir Nia reports that she has no conflicts of interest concerning the subject matter of this article.

The evidence for cannabidiol

Disclosures:

Cannabis is a complex plant with more than 100 types of cannabinoids. Its main psychoactive compound is δ-9-tetrahydrocannabinol (THC), which activates cannabinoid receptors to produce its “feeling high” effects. Cannabidiol (CBD) is another cannabinoid that has attracted growing attention recently. Unlike THC, CBD does not bind to cannabinoid receptors and has shown different, sometimes counteractive, effects. Currently, there are more than 100 clinical trials registered on the ClinicalTrials.gov website on the potential therapeutic effects of CBD.

6. Englund A, Morrison PD, Nottage J, et al. Cannabidiol inhibits THC-elicited paranoid symptoms and hippoc ampal-dependent memory impairment. J Psychopharmacol. 2013;27:19-27.

References:

Mechanism of action

Since then, the antipsychotic properties of CBD have been investigated in three clinical trials with mixed results (Table). In 2012, Leweke and colleagues 11 published the first double blind randomized controlled clinical trial on the therapeutic effects of CBD (600-800 mg/d for 4 weeks) compared with amisulpride on acute psychosis in individuals with schizophrenia (N = 42). The study concluded that CBD is as effective as amisulpride in treating psychotic symptoms and has fewer adverse effects, including less extra pyramidal symptoms and weight gain.

Cbd and schizophrenia

Indirect evidence for the antipsychotic and anxiolytic effects of CBD comes from preclinical studies, where specific features of psychotic disorders are modelled in animals and allow potential therapeutic effects to be examined from molecular to behavioural levels. 26

Hyperlocomotion

The reasons for the contrasting results with the two larger clinical trials remain unclear and warrant consideration. 53,55 One factor could be the lower CBD dose (600 mg/day) used by Boggs and colleagues, 56 compared with the higher doses of 800 and 1000 mg/day in the earlier trials. 53,55 While 600 mg (even as a single acute dose) has been shown to modulate brain function across a variety of tasks in healthy individuals, and can prevent the acute induction of psychotic symptoms following THC, 24 it is possible that a higher therapeutic dose is needed in the context of patients with psychosis. 56 This is consistent with the results from a further earlier study, which also used 600 mg/day in patients with schizophrenia, and which showed nonsignificant results for total PANSS symptom reduction, 54 although there were also a number of design issues associated with this study. Research conducted outside of the psychosis literature suggests that specific effects of CBD follow an inverted-U dose-response curve. This could have pragmatic implications for CBD as a novel pharmacotherapy because individual-patient dose titration would introduce practical challenges in the clinic. In two studies testing multiple doses of acute CBD against anxiety induced by public speaking, only the intermediate doses of CBD (300 mg) significantly reduced anxiety while lower and higher doses did not. 65,66 Animal models of anxiety confirm this dose-response effect, with anxiolytic effects observed at lower doses which disappear at higher doses. 12,67 However, the dose-response range is thought to be narrower for the anxiolytic compared with the antipsychotic effects of CBD, 67,68 at least in preclinical studies. 28 Higher doses are also likely required for antipsychotic versus anxiolytic effects (for review see Crippa and colleagues). 12 Future research is required to determine the precise dose-response ranges for specific therapeutic (i.e. antipsychotic and anxiolytic) effects for specific psychotic disorders and other clinical popluations. 12

Table 1.

ORCID iD: Cathy Davies https://orcid.org/0000-0003-3011-8643