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cbd psychosis

Pertwee RG (2008) The diverse CB 1 and CB 2 receptor pharmacology of three plant cannabinoids: Δ 9-tetrahydrocannabinol, cannabidiol and Δ 9-tetrahydrocannabivarin. Br J Pharmacol 153:199–215. https://doi.org/10.1038/sj.bjp.0707442

Leweke FM, Hellmich M, Pahlisch F et al (2014) Modulation of the endocannabinoid system as a potential new target in the treatment of schizophrenia. Schizophr Res 153:S47. https://doi.org/10.1016/s0920-9964(14)70153-7

Robinson SM, Sobell LC, Sobell MB, Leo GI (2014) Reliability of the Timeline Followback for cocaine, cannabis, and cigarette use. Psychol Addict Behav 28:154–162. https://doi.org/10.1037/a0030992

Corresponding author

Ryberg E, Larsson N, Sjögren S et al (2007) The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol 152:1092–1101. https://doi.org/10.1038/sj.bjp.0707460

Schoeler T, Monk A, Sami MB et al (2016) Continued versus discontinued cannabis use in patients with psychosis: a systematic review and meta-analysis. Lancet Psychiatry 3:215–225. https://doi.org/10.1016/S2215-0366(15)00363-6

Accepted : 15 June 2021

Funding

O’Neill A, Annibale L, Blest-Hopley G et al (2021) Cannabidiol modulation of hippocampal glutamate in early psychosis. J Psychopharmacol 02698811211001107. https://doi.org/10.1177/02698811211001107

McPartland JM, Duncan M, Di Marzo V, Pertwee RG (2015) Are cannabidiol and Δ9-tetrahydrocannabivarin negative modulators of the endocannabinoid system? A systematic review. Br J Pharmacol 172:737–753. https://doi.org/10.1111/bph.12944

Cbd psychosis

Further evidence for the protective effects of CBD against the psychotomimetic, anxiogenic, and cognition-impairing effects of THC comes from experimental studies where the two cannabinoids have been co-administered. THC can be used as an experimental model of psychosis in humans because its acute administration in healthy individuals can induce transient psychotic-like symptoms (including both positive and negative symptoms), as well as cognitive deficits resembling those seen in schizophrenia. 41 –47 In one study, six healthy volunteers received intravenous THC (1.25 mg) on two occasions, once preceded by intravenous placebo and once by CBD (2.5 mg) in a double-blind, within-subject design. 24 At the group level, THC administration with placebo pretreatment was associated with transient psychotomimetic effects, which was not observed under the CBD pretreatment condition. 24 A larger between-group study (n = 48) showed that relative to placebo, pretreatment with 600 mg oral CBD reduced the paranoia and impairments in episodic memory elicited by 1.5 mg intravenous THC. 23

More recently, in a 6-week multicentre, randomised, double-blind, parallel-group trial, CBD (1000 mg/day; n = 43) was compared with placebo (n = 45) as an add-on treatment to existing antipsychotic regimens in patients with schizophrenia. 55 There was a significant reduction in PANSS positive symptoms from baseline to 6-week study endpoint in the CBD compared with the placebo group (PANSS treatment difference = −1.4, 95% CI = −2.5 to −0.2; p = 0.019). CBD-treated patients were also more likely to have been rated as improved (Clinical Global Impression Scale; CGI-I treatment difference = −0.5, 95% CI = −0.8 to −0.1; p = 0.018) and as not severely unwell (–0.3, 95% CI = −0.5 to 0.0; p = 0.044) by the treating clinician. 55 Although the magnitude of these effects appears modest, it is common for treatments to fail in add-on trial designs because the tested treatment needs to show an effect over and above that of the existing treatment (here, antipsychotics, which have relatively large effect sizes). 4,63,64 The fact that CBD produced such an additional effect over that of concomitant antipsychotic treatment is therefore promising. There were also numerical (but nonsignificant) increases in the level of general functioning [Global Assessment of Functioning (GAF) scale treatment difference = 3.0, 95% CI = −0.4 to 6.4; p = 0.08] and cognitive performance in the CBD treatment arm compared with the placebo arm, but no significant differences emerged in a number of other outcomes, including on negative, total and general PANSS scores. 55 The number of adverse events was similar between the CBD (30 adverse events in 15 patients) and the placebo (35 adverse events in 16 patients) treatment arms, with the most common side effects including diarrhoea, nausea and headache. Most side effects were mild and did not require intervention.

Human experimental and neuroimaging studies

Using a randomised, double-blind, placebo-controlled, parallel-arm design, 33 antipsychotic-naive individuals at clinical high risk for psychosis and 19 healthy controls were studied using a verbal learning fMRI task. 57 A total of 16 high-risk subjects received a single oral dose of CBD (600 mg) and 17 received placebo. Control participants were not given any drug. The results showed that a single dose of CBD normalised brain function in clinical high-risk individuals in regions where high-risk individuals showed abnormal activation under placebo conditions. These specific regions, including the hippocampus, midbrain and striatum, are also strongly implicated in the pathophysiology of psychosis onset. 75,76 The normalisation of aberrant brain function in these regions by CBD could underlie the therapeutic effects observed in previous studies in patients with established psychosis and anxiety disorders. 53,55,77

Initial studies

A meta-analysis of studies conducted in epilepsy found that CBD was associated with significantly increased serum aminotransferases, with a risk ratio of 14.14 (95% CI = 4.48–44.60) in studies using 20 mg/kg CBD. 91 While the potential for hepatic toxicity was identified in this meta-analysis, no events within the individual studies met criteria for lasting liver injury (i.e. based on bilirubin). 91 Monitoring of hepatic function, particularly during the first 30 days of treatment, is therefore recommended. 91,95 Given the potentially serious nature and consequences of this potential side effect, future research should attempt to evaluate such effects (and in additional patient populations).