Acute Effects of Cannabis on Symptoms of Obsessive-Compulsive Disorder

Journal of Affective Disorders“Background: Little is known about the the acute effects of cannabis on symptoms of OCD in humans. Therefore, this study sought to: 1) examine whether symptoms of OCD are significantly reduced after inhaling cannabis, 2) examine predictors (gender, dose, cannabis constituents, time) of these symptom changes and 3) explore potential long-term consequences of repeatedly using cannabis to self-medicate for OCD symptoms, including changes in dose and baseline symptom severity over time.

Results: Patients reported a 60% reduction in compulsions, a 49% reduction in intrusions, and a 52% reduction in anxiety from before to after inhaling cannabis. Higher concentrations of CBD and higher doses predicted larger reductions in compulsions. The number of cannabis use sessions across time predicted changes in intrusions, such that later cannabis use sessions were associated with smaller reductions in intrusions. Baseline symptom severity and dose remained fairly constant over time.

Conclusions: Inhaled cannabis appears to have short-term beneficial effects on symptoms of OCD. However, tolerance to the effects on intrusions may develop over time.”

https://pubmed.ncbi.nlm.nih.gov/33049434/

“Inhaled cannabis reduced the severity of compulsions by 60% and intrusions by 49%.”

https://www.sciencedirect.com/science/article/abs/pii/S0165032720328202?via%3Dihub

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Cannabis Improves Obsessive-Compulsive Disorder-Case Report and Review of the Literature

Archive of "Frontiers in Psychiatry". “Although several lines of evidence support the hypothesis of a dysregulation of serotoninergic neurotransmission in the pathophysiology of obsessive-compulsive disorder (OCD), there is also evidence for an involvement of other pathways such as the GABAergic, glutamatergic, and dopaminergic systems.

Only recently, data obtained from a small number of animal studies alternatively suggested an involvement of the endocannabinoid system in the pathophysiology of OCD reporting beneficial effects in OCD-like behavior after use of substances that stimulate the endocannabinoid system.

In humans, until today, only two case reports are available reporting successful treatment with dronabinol (tetrahydrocannabinol, THC), an agonist at central cannabinoid CB1 receptors, in patients with otherwise treatment refractory OCD. In addition, data obtained from a small open uncontrolled trial using the THC analogue nabilone suggest that the combination of nabilone plus exposure-based psychotherapy is more effective than each treatment alone.

These reports are in line with data from a limited number of case studies and small controlled trials in patients with Tourette syndrome (TS), a chronic motor and vocal tic disorder often associated with comorbid obsessive compulsive behavior (OCB), reporting not only an improvement of tics, but also of comorbid OCB after use of different kinds of cannabis-based medicines including THC, cannabis extracts, and flowers.

Here we present the case of a 22-year-old male patient, who suffered from severe OCD since childhood and significantly improved after treatment with medicinal cannabis with markedly reduced OCD and depression resulting in a considerable improvement of quality of life. In addition, we give a review of current literature on the effects of cannabinoids in animal models and patients with OCD and suggest a cannabinoid hypothesis of OCD.”

https://pubmed.ncbi.nlm.nih.gov/32848902/

https://www.frontiersin.org/articles/10.3389/fpsyt.2020.00681/full

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The Endocannabinoid System: A New Treatment Target for Obsessive Compulsive Disorder?

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“Obsessive-compulsive disorder (OCD) is a disabling illness that is associated with significant functional impairment. Although evidence-based pharmacotherapies exist, currently available medications are ineffective in some patients and may cause intolerable side effects in others. There is an urgent need for new treatments.

Discussion: A growing body of basic and clinical research has showed that the endocannabinoid system (ECS) plays a role in anxiety, fear, and repetitive behaviors. At the same time, some patients with OCD who smoke cannabis anecdotally report that it relieves their symptoms and mitigates anxiety, and several case reports describe patients whose OCD symptoms improved after they were treated with cannabinoids. Taken together, these findings suggest that the ECS could be a potential target for novel medications for OCD. In this study, we review evidence from both animal and human studies that suggests that the ECS may play a role in OCD and related disorders. We also describe findings from studies in which cannabinoid drugs were shown to impact symptoms of these conditions.

Recent studies in both humans and animals have shown a critical role for the ECS in anxiety, stress, fear, and repetitive/habitual behaviors. Moreover, many patients with OCD who use cannabis anecdotally report that it improves their symptoms and reduces anxiety.

Conclusions: An emerging body of evidence suggests that the ECS plays a role in OCD symptoms and may be a target for the development of novel medications. Further exploration of this topic through well-designed human trials is warranted.”

https://www.liebertpub.com/doi/10.1089/can.2018.0049

“Can cannabinoids help treat obsessive-compulsive disorder?”  https://eurekalert.org/pub_releases/2019-05/mali-cch053119.php

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Plasma and brain pharmacokinetic profile of cannabidiol (CBD), cannabidivarine (CBDV), Δ⁹-tetrahydrocannabivarin (THCV) and cannabigerol (CBG) in rats and mice following oral and intraperitoneal administration and CBD action on obsessive-compulsive behaviour.

 

Psychopharmacology

“Phytocannabinoids are useful therapeutics for multiple applications including treatments of constipation, malaria, rheumatism, alleviation of intraocular pressure, emesis, anxiety and some neurological and neurodegenerative disorders.

Consistent with these medicinal properties, extracted cannabinoids have recently gained much interest in research, and some are currently in advanced stages of clinical testing.

Other constituents of Cannabis sativa, the hemp plant, however, remain relatively unexplored in vivo. These include cannabidiol (CBD), cannabidivarine (CBDV), Δ(9)-tetrahydrocannabivarin (Δ(9)-THCV) and cannabigerol (CBG).

RESULTS:

All phytocannabinoids readily penetrated the blood-brain barrier and solutol, despite producing moderate behavioural anomalies, led to higher brain penetration than cremophor after oral, but not intraperitoneal exposure. In mice, cremophor-based intraperitoneal administration always attained higher plasma and brain concentrations, independent of substance given. In rats, oral administration offered higher brain concentrations for CBD (120 mg/kg) and CBDV (60 mg/kg), but not for Δ(9)-THCV (30 mg/kg) and CBG (120 mg/kg), for which the intraperitoneal route was more effective. CBD inhibited obsessive-compulsive behaviour in a time-dependent manner matching its pharmacokinetic profile.

CONCLUSIONS:

These data provide important information on the brain and plasma exposure of new phytocannabinoids and guidance for the most efficacious administration route and time points for determination of drug effects under in vivo conditions.”

http://www.ncbi.nlm.nih.gov/pubmed/21796370

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A frequent polymorphism in the coding exon of the human cannabinoid receptor (CNR1) gene.

“The central cannabinoid receptor (CB1) mediates the pharmacological activities of cannabis, the endogenous agonist anandamide and several synthetic agonists.

The cloning of the human cannabinoid receptor (CNR1) gene facilitates molecular genetic studies in disorders like Gilles de la Tourette syndrome (GTS), obsessive compulsive disorder (OCD), Parkinsons disease, Alzheimers disease or other neuro psychiatric or neurological diseases, which may be predisposed or influenced by mutations or variants in the CNR1 gene.

We detected a frequent silent mutation (1359G–>A) in codon 453 (Thr) of the CNR1 gene that turned out to be a common polymorphism in the German population. Allele frequencies of this polymorphism are 0.76 and 0.24, respectively.

We developed a simple and rapid polymerase chain reaction (PCR)-based assay by artificial creation of a Msp I restriction site in amplified wild-type DNA (G-allele), which is destroyed by the silent mutation (A-allele).

The intragenic CNR1 polymorphism 1359(G/A) should be useful for association studies in neuro psychiatric disorders which may be related to anandamide metabolism disturbances.”

http://www.ncbi.nlm.nih.gov/pubmed/10441206

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Endocannabinoid analogues exacerbate marble-burying behavior in mice via TRPV1 receptor.

“Activation of cannabinoid CB(1) receptor is shown to inhibit marble-burying behavior (MBB), a behavioral model for assessing obsessive-compulsive disorder (OCD).

Anandamide, an endogenous agonist at CB(1) receptor also activates the transient receptor potential vanilloid type 1 (TRPV1) channels but at a higher concentration.

Furthermore, anandamide-mediated TRPV1 effects are opposite to that of the CB(1) receptor. Therefore, the present study was carried out to investigate the influence of low and high doses of anandamide on MBB in CB(1) and TRPV1 antagonist pre-treated mice.

Thus, the study indicates the biphasic influence of anandamide on MBB, and chronic administration of capsazepine either alone or with URB597 might be an effective tool in the treatment of OCD.”

http://www.ncbi.nlm.nih.gov/pubmed/22248639

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Facilitation of CB1 receptor-mediated neurotransmission decreases marble burying behavior in mice.

“Obsessive-compulsive disorder (OCD) is a common psychiatric disorder characterized by the occurrence of obsessions and compulsions.

Glutamatergic abnormalities have been related to the pathophysiology of OCD.

Cannabinoids inhibit glutamate release in the central nervous system, but the involvement of drugs targeting the endocannabinoid system has not yet been tested in animal models of repetitive behavior.

Thus, the aim of the present study was to verify the effects of the CB1 receptor agonist WIN55,212-2, the inhibitor of anandamide uptake AM404 and the anandamide hydrolysis inhibitor URB597, on compulsive-associate behavior in male C57BL/6J mice submitted to the marble burying test (MBT), an animal model used for anti-compulsive drug screening.

These results suggest a potential role for drugs acting on the cannabinoid system in modulating compulsive behavior.”

http://www.ncbi.nlm.nih.gov/pubmed/21111767

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Cannabidiol inhibitory effect on marble-burying behaviour: involvement of CB1 receptors.

“Cannabidiol (CBD) is a major non-psychotomimetic component of Cannabis sativa that has been shown to have an anxiolytic effect in human and animal models.

Earlier studies suggest that these effects involve facilitation of serotonin, a neurotransmitter that has also been related to obsessive-compulsive disorder.

On the basis of this evidence, this study investigated the effects of CBD in C57BL/6J mice submitted to the marble-burying test (MBT), an animal model proposed to reflect compulsive behaviour.

CBD induced a significant decrease in the number of buried marbles compared with controls.

These results indicated that CBD and paroxetine decrease the number of buried marbles in the MBT through distinct pharmacological mechanisms.

They also suggest a potential role of drugs acting on the cannabinoid system in modulating compulsive behaviour.”

http://www.ncbi.nlm.nih.gov/pubmed/20695034

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Study: Non-Psychoactive Cannabis Could Treat OCD

Leaf Science

“A non-psychoactive chemical in marijuana may be able to control symptoms of obsessive-compulsive disorder, according to new research out of Brazil.

Cannabidiol (CBD) is one of the major compounds found in marijuana, but lacks the high caused by THC.

Previous studies suggest that it can be used to combat anxiety and other obsessive-compulsive behaviors.

While research has mostly involved simple animal models, a team led by Dr. Francisco Guimarães of the University of Sao Paulo’s School of Medicine decided to test cannabidiol in rats that were given mCPP – a drug that blocks the effects of traditional OCD treatments.

Interestingly, even at low doses, CBD was able to reverse the obsessive-compulsive behavior caused by mCPP. Published in the journal Fundamental & Clinical Pharmacology, the authors conclude that the study adds support to “a possible anti-compulsive effect of CBD.””

http://www.leafscience.com/2013/10/22/study-non-psychoactive-cannabis-treat-ocd/

“Cannabidiol reverses the mCPP-induced increase in marble-burying behavior.”  http://www.ncbi.nlm.nih.gov/pubmed/24118015

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Cannabidiol reverses the mCPP-induced increase in marble-burying behavior

Fundamental & Clinical Pharmacology

“Cannabidiol (CBD), one of the main components of Cannabis sp., presents clinical and preclinical anxiolytic properties.

Recent results using the marble-burying test (MBT) suggest that CBD can also induce anticompulsive-like effects.

The results, in addition to reinforcing a possible anticompulsive effect of CBD, also suggest that mCPP-induced repetitive burying could be a useful test for the screening of compounds with presumed anticompulsive properties.”

http://onlinelibrary.wiley.com/doi/10.1111/fcp.12051/abstract

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