Background: A high prevalence of cannabis use disorder has been reported in subjects suffering from schizophrenia, fueling intense debate about whether schizophrenia with pre-onset cannabis use disorder may be a distinct entity with specific features or whether cannabis use disorder can precipitate schizophrenia in genetically vulnerable subjects. Methods: We retrospectively assessed schizophrenia subjects with and without pre-onset cannabis use disorder on the basis of their clinical features, assessed categorically and dimensionally with the operational criteria checklist for psychotic illnesses (OCCPI). We also investigated whether the two groups could be differentiated on the basis of a history of psychiatric disorders in first-degree relatives. A principal...

Conditions have been worked out for a reliable estimation of the cataleptic activity of delta'-trans-tetrahydrocannabinol (THC) after oral administration to mice, using the ring test over a period of 6 h. By this method, the activity of cannabis herb and 5 crude fractions were measured against THC; at the same time the THC contents were determined chemically. The B/C ratio (biological activity divided by chemical assay) was calculated for each. With cannabis herb the value was 3.3 and with extracts prepared with ethanol or 70% ethanol the values ranged from 3.2 to 7.1, indicating that in all samples the activity was much higher than...

Cannabidiol is a component of marijuana that does not activate cannabinoid receptors, but moderately inhibits the degradation of the endocannabinoid anandamide. We previously reported that an elevation of anandamide levels in  cerebrospinal fluid inversely correlated to psychotic symptoms. Furthermore, enhanced anandamide signaling let to a lower transition rate from initial prodromal states into frank psychosis as well as postponed transition. In our translational approach, we performed a double-blind, randomized clinical trial of cannabidiol vs amisulpride, a potent antipsychotic, in acute schizophrenia to evaluate the clinical relevance of our initial findings. Either treatment was safe and led to significant clinical improvement, but cannabidiol displayed a...

Cannabidiol (CBD), a major phytocannabinoid constituent of cannabis, is attracting growing attention in medicine for its anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties. However, up to this point, a comprehensive literature review of the effects of CBD in humans is lacking. The aim of the present systematic review is to examine the randomized and crossover studies that administered CBD to healthy controls and to clinical patients. A systematic search was performed in the electronic databases PubMed and EMBASE using the key word “cannabidiol”. Both monotherapy and combination studies (e.g., CBD + ∆9-THC) were included. A total of 34 studies were identified: 16 of these were...

Cannabidiol, a nonpsychoactive constituent of the Cannabis sativa plant, has been reported to act as an agonist of the vanilloid 1 channel in the transient receptor potential family (TRPV1) and also to inhibit the hydrolysis and cellular uptake of the endogenous cannabinoid anandamide. Cannabidiol has also been reported to have potential as an antipsychotic. We investigated the effect of cannabidiol on sensorimotor gating deficits in mice induced by the noncompetitive NMDA receptor antagonist, MK-801. Sensorimotor gating is deficient in psychotic disorders such as schizophrenia and may be reliably measured by prepulse inhibition (PPI) of the startle response in rodents and humans. MK-801 (0.3–1 mg/kg...

Endocannabinoids and their receptors, mainly the CB1 receptor type, function as a retrograde signaling system in many synapses within the CNS, particularly in GABAergic and glutamatergic synapses. They also play a modulatory function on dopamine (DA) transmission, although CB1 receptors do not appear to be located in dopaminergic terminals, at least in the major brain regions receiving dopaminergic innervation, e.g., the caudate-putamen and the nucleus accumbens/prefrontal cortex. Therefore, the effects of cannabinoids on DA transmission and DA-related behaviors are generally indirect and exerted through the modulation of GABA and glutamate inputs received by dopaminergic neurons. Recent evidence suggest, however, that certain eicosanoid-derived cannabinoids may...

Abstract Background Levels of cannabinoid 1 receptor (CB1R) mRNA and protein, which are expressed most heavily in the cholecystokinin class of GABA neurons, are lower in the dorsolateral prefrontal cortex (DLPFC) in schizophrenia, and the magnitude of these differences is strongly correlated with that for glutamic acid decarboxylase (GAD67) mRNA, a synthesizing enzyme for GABA. However, whether this correlation reflects a cause-effect relationship is unknown. Methods Using quantitative in situ hybridization, we measured CB1R, GAD67, and diacylglycerol lipase alpha (DAGLα; the synthesizing enzyme for the endocannabinoid 2-arachidonoylglycerol) mRNA levels in the medial prefrontal cortex of genetically-engineered GAD67 heterozygous (GAD67+/−), CB1R heterozygous (CB1R+/−), CB1R knockout (CB1R−/−), and matched...

Cannabis contains various cannabinoids, two of which have almost opposing actions: D9-tetrahydrocannabinol (D9-THC) is psychotomimetic, whereas cannabidiol (CBD) has antipsychotic effects. Hair samples were analysed to examine levels of D9-THC and CBD in 140 individuals. Three clear groups emerged: ‘THC only’, ‘THC+CBD’ and those with no cannabinoid in hair. The THC only group showed higher levels of positive schizophrenia-like symptoms compared with the no cannabinoid and THC+CBD groups, and higher levels of delusions compared with the no cannabinoid group. This provides evidence of the divergent properties of cannabinoids and has important implications for research into the link between cannabis use and psychosis.

Cannabidiol (CBD), a once-considered inert cannabis constituent, is one of two primary constituents of cannabis, alongside delta-9-tetrahydrocannabinol (∆9-THC/THC). In the last 30 years, CBD has become implicated with a range of pharmaceutical mechanisms of great therapeutic interest and utility. This review details the literature speculating CBD’s attenuation of psychotic symptoms, particularly in light of a marked elevation in mean THC concentrations, and a concomitant decline in CBD concentrations in the prevalent U.K street market cannabis derivatives since c. 2000. CBD is purported to exhibit pharmacology akin to established atypical antipsychotics, whilst THC has been implicated with the precipitation of psychosis, and the induction of...