Cannabis Use and Psychosis: A Longitudinal Population-based Study

896

678

Recent advances in the understanding of brain cannabinoid receptor function have renewed interest in the association between cannabinoid compounds and psychosis. In a 3-day, double-blind, randomized, and counterbalanced study, the behavioral, cognitive, and endocrine effects of 0, 2.5, and 5 mg intravenous delta-9-tetrahydrocannabinol (D-9-THC) were characterized in 22 healthy individuals, who had been exposed to cannabis but had never been diagnosed with a cannabis abuse disorder. Prospective safety data at 1, 3, and 6 months poststudy was also collected. D-9-THC (1) produced schizophrenia-like positive and negative symptoms; (2) altered perception; (3) increased anxiety; (4) produced euphoria; (5) disrupted immediate and delayed word recall, sparing recognition recall; (6) impaired performance on tests of distractibility, verbal fluency, and working memory (7) did not impair orientation; (8) increased plasma cortisol. These data indicate that D-9-THC produces a broad range of transient symptoms, behaviors, and cognitive deficits in healthy individuals that resemble some aspects of endogenous psychoses. These data warrant further study of whether brain cannabinoid receptor function contributes to the pathophysiology of psychotic disorders.

Section: Discussionmentioning

confidence: 99%

The Psychotomimetic Effects of Intravenous Delta-9-Tetrahydrocannabinol in Healthy Individuals: Implications for Psychosis

D’Souza

Perry

MacDougall

et al. 2004

896

678

“…Clinical evidence has confirmed such links. Early-onset cannabis use increases the risk of developing schizophrenia (Arseneault et al, 2002;Fergusson et al, 2003;van Os et al, 2002) as well as a worsen course of the disorder (Green et al, 2004;Veen et al, 2004). Several epidemiological studies report that early regular use of cannabis increases the risk of initiation of the use of other illicit drugs (Agrawal et al, 2004;Fergusson and Horwood, 2000;Lynskey et al, 2003;Yamaguchi and Kandel, 1984), supporting the cannabis gateway hypothesis of cannabis as a steppingstone toward abuse of other drugs.…”

Section: Introductionmentioning

confidence: 93%

Adolescent Cannabis Exposure Alters Opiate Intake and Opioid Limbic Neuronal Populations in Adult Rats

Ellgren

Spano

Hurd

2006

258

208

Cannabis use is a hypothesized gateway to subsequent abuse of other drugs such as heroin. We currently assessed whether D-9-tetrahydrocannabinol (THC) exposure during adolescence modulates opiate reinforcement and opioid neural systems in adulthood. Long-Evan male rats received THC (1.5 mg/kg intraperitoneally (i.p.)) or vehicle every third day during postnatal days (PNDs) 28-49. Heroin self-administration behavior (fixed ratio-1; 3-h sessions) was studied from young adulthood (PND 57) into full adults (PND 102). THC-pretreated rats showed an upward shift throughout the heroin self-administration acquisition (30 mg/kg/infusion) phase, whereas control animals maintained the same pattern once stable intake was obtained. Heightened opiate sensitivity in THC animals was also evidenced by higher heroin consumption during the maintenance phase (30 and 60 mg/kg/infusion) and greater responding for moderate-low heroin doses (dose-response curve: 7.5, 15, 30, 60, and 100 mg/kg/injection). Specific disturbance of the endogenous opioid system was also apparent in the brain of adults with adolescent THC exposure. Striatal preproenkephalin mRNA expression was exclusively increased in the nucleus accumbens (NAc) shell; the relative elevation of preproenkephalin mRNA in the THC rats was maintained even after heroin self-administration. Moreover, m opioid receptor (mOR) GTP-coupling was potentiated in mesolimbic and nigrostriatal brainstem regions in THC-pretreated animals. mOR function in the NAc shell was specifically correlated to heroin intake. The current findings support the gateway hypothesis demonstrating that adolescence cannabis exposure has an enduring impact on hedonic processing resulting in enhanced opiate intake, possibly as a consequence of alterations in limbic opioid neuronal populations.

“…Previous work has shown that subclinical psychotic experiences measured with valid self-report questionnaires show longitudinal continuity with more severe states of psychosis, such as psychotic illness (Chapman et al, 1994;Hanssen et al, 2005) and are transmitted in families . Similarly, established risk factors for psychotic illness also affect the occurrence of these subclinical psychotic experiences (Krabbendam et al, 2005;Nuechterlein et al, 2002;van Os et al, 2002van Os et al, , 2000van Os et al, , 2001. Subclinical psychotic experiences as measured with the CAPE can therefore be considered as a proxy for an underlying liability to psychosis (Johns and van Os, 2001).…”

Section: Psychosis Measuresmentioning

confidence: 99%

An Experimental Study of Catechol-O-Methyltransferase Val158Met Moderation of Δ-9-Tetrahydrocannabinol-Induced Effects on Psychosis and Cognition

Henquet

Rosa

Krabbendam

et al. 2006

285

210

Observational studies have suggested that psychometric psychosis liability and a functional polymorphism in the catechol-Omethyltransferase (COMT Val 158 Met) gene moderate the psychosis-inducing effect of cannabis. To replicate and extend this finding, a double-blind, placebo-controlled cross-over design was used in which patients with a psychotic disorder (n ¼ 30), relatives of patients with a psychotic disorder (n ¼ 12), and healthy controls (n ¼ 32) were exposed to D-9-tetrahydrocannabinol (D-9-THC, the principal component of cannabis) or placebo, followed by cognitive assessment and assessment of current psychotic experiences. Previous expression of psychometric psychosis liability was also assessed. Models of current psychotic experiences and cognition were examined with multilevel random regression analyses to assess (i) main effects of genotype and condition, (ii) interactions between condition and genotype, and (iii) three-way interactions between condition, genotype, and psychometric psychosis liability. Carriers of the Val allele were most sensitive to D-9-THC-induced psychotic experiences, but this was conditional on prior evidence of psychometric psychosis liability. D-9-THC impacted negatively on cognitive measures. Carriers of the Val allele were also more sensitive to D-9-THC-induced memory and attention impairments compared to carriers of the Met allele. Experimental effects of D-9-THC on cognition and psychosis are moderated by COMT Val 158 Met genotype, but the effects may in part be conditional on the additional presence of pre-existing psychosis liability. The association between cannabis and psychosis may represent higher order gene-environment and gene-gene interactions.