Substance-induced psychosis & schizophrenia

Many physicians and patients worry that medical cannabis may trigger drug-induced psychosis or schizophrenia. Cannabis-induced psychosis, which symptomatically is similar to psychotic episodes of paranoid schizophrenia, at least shows a more favorable prognosis compared to other drug-related psychoses (also alcohol). It is no news that regular use of cannabis correlates with schizophrenic diseases, especially when already used during puberty. However, it is less well-known that this connection is not causal but only correlative. Psychologic disorders like schizophrenia are triggered by various acute and chronic stressors (e.g. social, psychological, biological) along with an increased “susceptibility” (due to genetic, cognitive and also external factors). In contrast to THC cannabidiol (CBD) from the cannabis plant shows antipsychotic properties along with a more favorable profile in terms of side-effects than conventional neuroleptic drugs.

The group of disorders called psychoses is summarized as diseases that, inter alia, are related to loss of reality, delusions and erroneous thought, speech and emotion. Drug-related psychosis is caused by the use of drugs (cocaine, heroin, amphetamines, hallucinogens, alcohol or cannabis), partially after the first time of use. Psychoses can be irreversible or progress chronically, when the administration of the causing drug is not discontinued. The psychotic course and symptoms depend on the inducing drug. Psychoses are distinguished into predominantly hallucinatory, predominantly affective, predominantly polymorphous, predominantly delusional and schizophrenic subtypes. Cannabis-induced psychosis resembles the psychotic episodes of paranoid schizophrenia; therefore, an exact distinction based only on the observational analysis of the patient is complicated. Compared to all other mentioned drug-induced psychoses, a cannabis-induced psychosis at least has the most favorable prognosis.1

In contrast to “real” psychiatric primary diseases like schizophrenia, drug users showing psychotic symptoms during intoxication realize that the perceived hallucinations are caused by the drug and hence are not real. Quasi-psychotic, temporary conditions that are caused e.g. by administration of psychedelics (serotonergic hallucinogens like LSD or psilocybin) and entactogens (like MDMA) not only seem to provide pathologic but also therapeutic opportunities according to new scientific discoveries and are currently undergoing a renaissance in basic and clinical research.2,3,4

It is no news that regular use of cannabis correlates with schizophrenia, especially when cannabis use already started during puberty. However, it is less well-known that this relation is likely not causal (meaning that cannabis use causes schizophrenia) but only correlates (meaning that individuals that are challenged psychologically / genetically have an increased tendency to change their state of consciousness with mind-altering drugs, compared to healthy individuals).5,6

According to the generally accepted diathesis-stress model by Nüchterlein and Liberman psychological disorders are triggered by various acute and chronic stressors (e.g. social, psychological, biological) in the context of an increased “susceptibility” (due to genetic, cognitive and also external factors), see Fig. 1.

Fig. 1 Vulnerability-Stress-Coping-Competence Model (adapted from: Nüchterlein and Dawson, 1984)

It is known from post-mortem investigations and modern imaging techniques (MRT, PET) that the brains of schizophrenic patients show histo-architectural abnormalities, for example qualitative as well as quantitative alterations primarily in the temporal lobes, frontal lobes and ventricles. It is very unlikely that these kind of alterations are caused by the use of cannabis, which is known to merely modulate neurotransmission. Due to several identified gene mutations that correlate with schizophrenia and also relationship studies showing that susceptibility to schizophrenia is hereditary, a scenario of a fundamentally defective neuronal development or psychosocial factors is more likely for the etiology of the disease.7

A study8 published in 2018 even compared maternal and paternal cannabis use during pregnancy in order to investigate the causal effects of intra-uterine cannabis exposure during fetal neurological development. Interestingly, for the increased risk of psychotic episodes in the progeny it made no difference whether it was mother or father who consumed cannabis during pregnancy. This argues against a causal relationship of cannabis use.

Neuroleptics (reduce emotions and psychomotoric activity) primarily act on dopamine metabolism. Since dopaminergic neurotransmission strongly influences motor control, here the most severe side-effects can be observed (leading to symptoms similar to Parkinson´s disease). Other neuroleptics often lead to a strong increase in body weight and diabetes mellitus. These side-effects can be so grave that affected individuals often discontinue their treatment. Hence, scientists keep searching for modern pharmaceuticals with fewer side-effects.

Cannabidiol (CBD) is a naturally occurring component of the cannabis plant that – in contrast to THC – exhibits antipsychotic effects and counteracts the intoxicating effect of THC. Current scientific and clinical studies emphasize CBD´s potential for the treatment of a large number of diseases and disorders, inter alia, that of schizophrenia. In clinical studies an improved profile in terms of side-effects was demonstrated for CBD along with a stable antipsychotic effect (no gain of body weight, no prolactin increase, no movement dysfunctions). Amongst others, the Department of Psychiatry and Psychotherapy at the Charité hospital Berlin is currently investigating CBD for schizophrenia in more detail.10

[1] http://flexikon.doccheck.com/de/Drogenpsychose

[2] Carhart-Harris RL, Bolstridge M, Rucker J, et al. Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry. 2016;3(7):619-627. doi:10.1016/S2215-0366(16)30065-7

[3] Mithoefer MC, Mithoefer AT, Feduccia AA, et al. 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial. The Lancet Psychiatry. 2018;5(6):486-497. doi:10.1016/S2215-0366(18)30135-4

[4] Jungaberle H, Thal S, Zeuch A, et al. Positive psychology in the investigation of psychedelics and entactogens: A critical review. Neuropharmacology. June 2018. doi:10.1016/j.neuropharm.2018.06.034

[5] Pasman JA, Verweij KJH, Gerring Z, et al. GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal influence of schizophrenia. Nat Neurosci. August 2018:1. doi:10.1038/s41593-018-0206-1

[6] Manseau MW, Goff DC. Cannabinoids and Schizophrenia: Risks and Therapeutic Potential. Neurotherapeutics. 2015;12(4):816-824. doi:10.1007/s13311-015-0382-6

[7] Principles of Neuropsychopharmacology; Chapter 18: Schizophrenia. Robert S. Feldman, Jerrold S. Meyer, Linda F. Quenzer. ISBN-10: 0878931759; ISBN-13: 978-0878931750

[8] Bolhuis K, Kushner SA, Yalniz S, et al. Maternal and paternal cannabis use during pregnancy and the risk of psychotic-like experiences in the offspring. Schizophr Res. July 2018. doi:10.1016/j.schres.2018.06.067

[9] Schubart CD, Sommer IEC, van Gastel WA, Goetgebuer RL, Kahn RS, Boks MPM. Cannabis with high cannabidiol content is associated with fewer psychotic experiences. Schizophr Res. 2011;130(1-3):216-221. doi:10.1016/j.schres.2011.04.017

[10] https://www.esprit-berlin.de/cannabidiolstudie/