Category Archives: Schizophrenia

THC improves behavioural schizophrenia-like deficits that CBD fails to overcome: a comprehensive multilevel approach using the Poly I:C maternal immune activation

Posted on by
Reply
pubmed logo

“Prenatal infections and cannabis use during adolescence are well-recognized risk factors for schizophrenia. As inflammation and oxidative stress (OS) contribute to this disorder, anti-inflammatory drugs have been proposed as potential therapies. This study aimed to evaluate the association between delta-9-tetrahydrocannabinol (THC) and schizophrenia-like abnormalities in a maternal immune activation (MIA) model. Additionally, we assessed the preventive effect of cannabidiol (CBD), a non-psychotropic/anti-inflammatory cannabinoid. THC and/or CBD were administered to Saline- and MIA-offspring during periadolescence. At adulthood, THC-exposed MIA-offspring showed significant improvements in sensorimotor gating deficits. Structural and metabolic brain changes were evaluated by magnetic resonance imaging, revealing cortical shrinkage in Saline- and enlargement in MIA-offspring after THC-exposure. Additionally, MIA-offspring displayed enlarged ventricles and decreased hippocampus, which were partially reverted by both cannabinoids. CBD prevented THC-induced reduction in the corpus callosum, despite affecting white matter structure. Post-mortem studies revealed detrimental effects of THC, including increased inflammation and oxidative stress. CBD partially reverted these pro-inflammatory alterations and modulated THC’s effects on the endocannabinoid system. In conclusion, contrary to expectations, THC exhibited greater behavioural and morphometric benefits, despite promoting a pro-inflammatory state that CBD partially reverted. Further research is needed to elucidate the underlying mechanisms involved in the observed benefits of THC.”

https://pubmed.ncbi.nlm.nih.gov/38064909/

https://www.sciencedirect.com/science/article/abs/pii/S0165178123005930?via%3Dihub

The psychedelic effects of cannabis: A review of the literature

Posted on by
Reply
pubmed logo

“Cannabis and classic psychedelics are controlled substances with emerging evidence of efficacy in the treatment of a variety of psychiatric illnesses. Cannabis has largely not been regarded as having psychedelic effects in contemporary literature, despite many examples of historical use along with classic psychedelics to attain altered states of consciousness.

Research into the “psychedelic” effects of cannabis, and delta-9-tetrahydrocannabinol (THC) in particular, could prove helpful for assessing potential therapeutic indications and elucidating the mechanism of action of both cannabis and classic psychedelics.

This review aggregates and evaluates the literature assessing the capacity of cannabis to yield the perceptual changes, aversiveness, and mystical experiences more typically associated with classic psychedelics such as psilocybin. This review also provides a brief contrast of neuroimaging findings associated with the acute effects of cannabis and psychedelics.

The available evidence suggests that high-THC cannabis may be able to elicit psychedelic effects, but that these effects may not have been observed in recent controlled research studies due to the doses, set, and settings commonly used. Research is needed to investigate the effects of high doses of THC in the context utilized in therapeutic studies of psychedelics aimed to occasion psychedelic and/or therapeutic experiences.

If cannabis can reliably generate psychedelic experiences under these conditions, high-THC dose cannabis treatments should be explored as potential adjunctive treatments for psychiatric disorders and be considered as an active comparator in clinical trials involving traditional psychedelic medications.”

https://pubmed.ncbi.nlm.nih.gov/37947321/

https://journals.sagepub.com/doi/10.1177/02698811231209194

“Psychedelic drugs in the treatment of psychiatric disorders”

https://pubmed.ncbi.nlm.nih.gov/37615227/

Lack of interactions between prenatal immune activation and Δ9-tetrahydrocannabinol exposure during adolescence in behaviours relevant to symptom dimensions of schizophrenia in rats

Posted on by
Reply
pubmed logo

“The causality in the association between cannabis use and the risk of developing schizophrenia has been the subject of intense debate in the last few years. The development of animal models recapitulating several aspects of the disease is crucial for shedding light on this issue. Maternal infections are a known risk for schizophrenia. Here, we used the maternal immune activation (MIA) model combined with THC exposure during adolescence to examine several behaviours in rats (working memory in the Y maze, sociability in the three-chamber test, sucrose preference as a measure, prepulse inhibition and formation of incidental associations) that are similar to the different symptom clusters of the disease. To this end, we administered LPS to pregnant dams and when the offspring reached adolescence, we exposed them to a mild dose of THC to examine their behaviour in adulthood. We also studied several parameters in the dams, including locomotor activity in the open field, elevated plus maze performance and their response to LPS, that could predict symptom severity of the offspring, but found no evidence of any predictive value of these variables. In the adult offspring, MIA was associated with impaired working memory and sensorimotor gating, but surprisingly, it increased sociability, social novelty and sucrose preference. THC, on its own, impaired sociability and social memory, but there were no interactions between MIA and THC exposure. These results suggest that, in this model, THC during adolescence does not trigger or aggravate symptoms related to schizophrenia in rats.”

https://pubmed.ncbi.nlm.nih.gov/37918558/

https://www.sciencedirect.com/science/article/abs/pii/S0278584623001756?via%3Dihub

The therapeutic potential of purified cannabidiol

Posted on by
Reply
pubmed logo

“The use of cannabidiol (CBD) for therapeutic purposes is receiving considerable attention, with speculation that CBD can be useful in a wide range of conditions. Only one product, a purified form of plant-derived CBD in solution (Epidiolex), is approved for the treatment of seizures in patients with Lennox-Gastaut syndrome, Dravet syndrome, or tuberous sclerosis complex. Appraisal of the therapeutic evidence base for CBD is complicated by the fact that CBD products sometimes have additional phytochemicals (like tetrahydrocannabinol (THC)) present, which can make the identification of the active pharmaceutical ingredient (API) in positive studies difficult. The aim of the present review is to critically review clinical studies using purified CBD products only, in order to establish the upcoming indications for which purified CBD might be beneficial.

The areas in which there is the most clinical evidence to support the use of CBD are in the treatment of anxiety (positive data in 7 uncontrolled studies and 17 randomised controlled trials (RCTs)), psychosis and schizophrenia (positive data in 1 uncontrolled study and 8 RCTs), PTSD (positive data in 2 uncontrolled studies and 4 RCTs) and substance abuse (positive data in 2 uncontrolled studies and 3 RCTs). Seven uncontrolled studies support the use of CBD to improve sleep quality, but this has only been verified in one small RCT. Limited evidence supports the use of CBD for the treatment of Parkinson’s (3 positive uncontrolled studies and 2 positive RCTs), autism (3 positive RCTs), smoking cessation (2 positive RCTs), graft-versus-host disease and intestinal permeability (1 positive RCT each). Current RCT evidence does not support the use of purified oral CBD in pain (at least as an acute analgesic) or for the treatment of COVID symptoms, cancer, Huntington’s or type 2 diabetes.

In conclusion, published clinical evidence does support the use of purified CBD in multiple indications beyond epilepsy. However, the evidence base is limited by the number of trials only investigating the acute effects of CBD, testing CBD in healthy volunteers, or in very small patient numbers. Large confirmatory phase 3 trials are required in all indications.”

https://pubmed.ncbi.nlm.nih.gov/37312194/

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-023-00186-9

State Cannabis Legalization and Psychosis-Related Health Care Utilization

Posted on by
Reply
JAMA editors name the journal's best articles of the decade | American Medical Association

“Importance: Psychosis is a hypothesized consequence of cannabis use. Legalization of cannabis could therefore be associated with an increase in rates of health care utilization for psychosis.

Objective: To evaluate the association of state medical and recreational cannabis laws and commercialization with rates of psychosis-related health care utilization.

Design, setting, and participants: Retrospective cohort design using state-level panel fixed effects to model within-state changes in monthly rates of psychosis-related health care claims as a function of state cannabis policy level, adjusting for time-varying state-level characteristics and state, year, and month fixed effects. Commercial and Medicare Advantage claims data for beneficiaries aged 16 years and older in all 50 US states and the District of Columbia, 2003 to 2017 were used. Data were analyzed from April 2021 to October 2022.

Exposure: State cannabis legalization policies were measured for each state and month based on law type (medical or recreational) and degree of commercialization (presence or absence of retail outlets).

Main outcomes and measures: Outcomes were rates of psychosis-related diagnoses and prescribed antipsychotics.

Results: This study included 63 680 589 beneficiaries followed for 2 015 189 706 person-months. Women accounted for 51.8% of follow-up time with the majority of person-months recorded for those aged 65 years and older (77.3%) and among White beneficiaries (64.6%). Results from fully-adjusted models showed that, compared with no legalization policy, states with legalization policies experienced no statistically significant increase in rates of psychosis-related diagnoses (medical, no retail outlets: rate ratio [RR], 1.13; 95% CI, 0.97-1.36; medical, retail outlets: RR, 1.24; 95% CI, 0.96-1.61; recreational, no retail outlets: RR, 1.38; 95% CI, 0.93-2.04; recreational, retail outlets: RR, 1.39; 95% CI, 0.98-1.97) or prescribed antipsychotics (medical, no retail outlets RR, 1.00; 95% CI, 0.88-1.13; medical, retail outlets: RR, 1.01; 95% CI, 0.87-1.19; recreational, no retail outlets: RR, 1.13; 95% CI, 0.84-1.51; recreational, retail outlets: RR, 1.14; 95% CI, 0.89-1.45). In exploratory secondary analyses, rates of psychosis-related diagnoses increased significantly among men, people aged 55 to 64 years, and Asian beneficiaries in states with recreational policies compared with no policy.

Conclusions and relevance: In this retrospective cohort study of commercial and Medicare Advantage claims data, state medical and recreational cannabis policies were not associated with a statistically significant increase in rates of psychosis-related health outcomes. As states continue to introduce new cannabis policies, continued evaluation of psychosis as a potential consequence of state cannabis legalization may be informative.”

https://pubmed.ncbi.nlm.nih.gov/36696111/

“In this retrospective cohort study of commercial and Medicare Advantage claims data, state medical and recreational cannabis policies were not associated with a statistically significant increase in rates of psychosis-related health outcomes.”

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2800728

Regulation of DNA Methylation by Cannabidiol and Its Implications for Psychiatry: New Insights from In Vivo and In Silico Models

Posted on by
Reply
genes-logo

“Cannabidiol (CBD) is a non-psychotomimetic compound present in cannabis sativa. Many recent studies have indicated that CBD has a promising therapeutic profile for stress-related psychiatric disorders, such as anxiety, schizophrenia and depression. Such a diverse profile has been associated with its complex pharmacology, since CBD can target different neurotransmitter receptors, enzymes, transporters and ion channels. However, the precise contribution of each of those mechanisms for CBD effects is still not yet completely understood. Considering that epigenetic changes make the bridge between gene expression and environment interactions, we review and discuss herein how CBD affects one of the main epigenetic mechanisms associated with the development of stress-related psychiatric disorders: DNA methylation (DNAm). Evidence from in vivo and in silico studies indicate that CBD can regulate the activity of the enzymes responsible for DNAm, due to directly binding to the enzymes and/or by indirectly regulating their activities as a consequence of neurotransmitter-mediated signaling. The implications of this new potential pharmacological target for CBD are discussed in light of its therapeutic and neurodevelopmental effects.”

https://pubmed.ncbi.nlm.nih.gov/36421839/

https://www.mdpi.com/2073-4425/13/11/2165

Incidence and Predictors of Cannabis-Related Poisoning and Mental and Behavioral Disorders among Patients with Medical Cannabis Authorization: A Cohort Study

Posted on by
Reply
Publication Cover

“Objective: As medical cannabis use increases in North America, establishing its safety profile is a priority. The objective of this study was to assess rates of emergency department (ED) visits and hospitalizations due to poisoning by cannabis, and cannabis-related mental health disorders among medically authorized cannabis patients in Ontario, Canada, between 2014 and 2017.

Methods: This is a retrospective cohort study of patients who received medical cannabis authorization in Ontario, Canada, using data collected in participating cannabis clinics. Outcomes included ED visit/hospitalization with a main diagnosis code for: cannabis/cannabinoid poisoning; and mental/behavioral disorders due to cannabis use. Cox proportional hazard regressions were utilized to analyze the data.

Results: From 29,153 patients who received medical authorization, 23,091 satisfied the inclusion criteria. During a median follow-up of 240 days, 14 patients visited the ED or were hospitalized for cannabis poisoning-with an incidence rate of 8.06 per 10,000 person-years (95% CI: 4.8-13.6). A total of 26 patients visited the ED or were hospitalized for mental and behavioral disorders due to cannabis use-with an incidence rate of 15.0 per 10,000 person-years (95% CI: 10.2-22.0). Predictors of cannabis-related mental and behavioral disorders include prior substance use disorders, other mental disorders, age, diabetes, and chronic obstructive pulmonary disease.

Conclusions: The results suggest that the incidence of cannabis poisoning or cannabis-related mental and behavioral disorders was low among patients who were authorized to use cannabis for medical care. Identified predictors can help to target patients with potential risk of the studied outcomes.”

https://pubmed.ncbi.nlm.nih.gov/35866679/

https://www.tandfonline.com/doi/abs/10.1080/10826084.2022.2102193?journalCode=isum20

Inducing Effects of Illegal Drugs to Improve Mental Health by Self-Regulation Therapy: A Pilot Study

Posted on by
Reply

ijerph-logo“This study consists of a brief psychological intervention, which uses Self-Regulation Therapy (SRT, procedure based on suggestion and classical conditioning), to improve coping with stress and emotionality by reproducing the positive effects of illegal drugs: cannabis, cocaine, ecstasy.

Results: SRT was superior to non-intervention for the 4 coping strategies (η2 = 0.829, 0.453, 0.411 and 0.606) and for positive (η2 = 0.371) and negative emotionality (η2 = 0.419). An improvement in scores was evidenced in the follow-up scores compared to the pre-intervention measures.

Conclusions: This study shows for the first time that it is possible to use illegal drugs, considered harmful to public health, to improve young people’s coping capacity and emotionality by reproducing their positive effects with SRT.”

https://pubmed.ncbi.nlm.nih.gov/34639687/

https://www.mdpi.com/1660-4601/18/19/10387

A Review of the Potential Use of Pinene and Linalool as Terpene-Based Medicines for Brain Health: Discovering Novel Therapeutics in the Flavours and Fragrances of Cannabis

Posted on by
Reply

Archive of "Frontiers in Psychiatry".“”Medicinal cannabis” is defined as the use of cannabis-based products for the treatment of an illness. Investigations of cannabis compounds in psychiatric and neurological illnesses primarily focus on the major cannabinoids, cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC), which are hypothesised to benefit multiple illnesses manifesting cognitive impairment, neurodegeneration and neuro-inflammation, as well as chronic pain, epilepsy and post-traumatic stress disorder, respectively.

The cannabis plant contains >500 compounds, including terpenes responsible for the flavour and fragrance profiles of plants. Recently, research has begun providing evidence on the potential use of certain plant-derived terpenes in modern medicine, demonstrating anti-oxidant, anti-inflammatory, and neuroprotective effects of these compounds.

This review examined the effects of two key terpenes, pinene and linalool, on parameters relevant to neurological and psychiatric disorders, highlighting gaps in the literature and recommendations for future research into terpene therapeutics.

Overall, evidence is mostly limited to preclinical studies and well-designed clinical trials are lacking. Nevertheless, existing data suggests that pinene and linalool are relevant candidates for further investigation as novel medicines for illnesses, including stroke, ischemia, inflammatory and neuropathic pain (including migraine), cognitive impairment (relevant to Alzheimer’s disease and ageing), insomnia, anxiety, and depression.

Linalool and pinene influence multiple neurotransmitter, inflammatory and neurotrophic signals as well as behaviour, demonstrating psycho-activity (albeit non-intoxicating).   Optimising the phytochemical profile of cannabis chemovars to yield therapeutic levels of beneficial terpenes and cannabinoids, such as linalool, pinene and CBD, could present a unique opportunity to discover novel medicines to treat psychiatric and neurological illnesses; however, further research is needed.”

https://pubmed.ncbi.nlm.nih.gov/34512404/

“Overall, it appears that the importance of the terpene profile of plants to humans extends further than mere olfactory and gustatory delight. Rather, these compounds have the potential for use as treatments for serious chronic neurological and psychiatric illnesses.”

https://www.frontiersin.org/articles/10.3389/fpsyt.2021.583211/full

Cannabis sativa L. as a Natural Drug Meeting the Criteria of a Multitarget Approach to Treatment

Posted on by
Reply

ijms-logo“Cannabis sativa L. turned out to be a valuable source of chemical compounds of various structures, showing pharmacological activity. The most important groups of compounds include phytocannabinoids and terpenes.

The pharmacological activity of Cannabis (in epilepsy, sclerosis multiplex (SM), vomiting and nausea, pain, appetite loss, inflammatory bowel diseases (IBDs), Parkinson’s disease, Tourette’s syndrome, schizophrenia, glaucoma, and coronavirus disease 2019 (COVID-19)), which has been proven so far, results from the affinity of these compounds predominantly for the receptors of the endocannabinoid system (the cannabinoid receptor type 1 (CB1), type two (CB2), and the G protein-coupled receptor 55 (GPR55)) but, also, for peroxisome proliferator-activated receptor (PPAR), glycine receptors, serotonin receptors (5-HT), transient receptor potential channels (TRP), and GPR, opioid receptors.

The synergism of action of phytochemicals present in Cannabis sp. raw material is also expressed in their increased bioavailability and penetration through the blood-brain barrier. This review provides an overview of phytochemistry and pharmacology of compounds present in Cannabis extracts in the context of the current knowledge about their synergistic actions and the implications of clinical use in the treatment of selected diseases.”

https://pubmed.ncbi.nlm.nih.gov/33466734/

https://www.mdpi.com/1422-0067/22/2/778