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.”

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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.”

“Can cannabinoids help treat obsessive-compulsive disorder?”

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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.



“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).


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.


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.”

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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.”

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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.”

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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.”

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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.”

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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.””

“Cannabidiol reverses the mCPP-induced increase in marble-burying behavior.”

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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.”

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Cannabinoid Receptor Found to Help Suppress Habitual Behavior

“A mouse study finds that CB1 protein in orbitofrontal cortex neurons mediates the ability to switch between habitual and active-learning behaviors when needed.

Everyone carries out daily habits and routines. As David Lovinger, Ph.D., chief of the Laboratory for Integrative Neuroscience at the National Institute on Alcohol Abuse and Alcoholism (NIAAA), explained, “If your brain does not habitualize familiar tasks or places, it would be very difficult to focus because you’re constantly processing all these sensory inputs.”

Nonetheless, it’s important that the brain can shift from habit mode to a more active, goal-directed mindset. While an occasional lapse is normal, a chronic inability to exit from habitual behavior is a critical element of both addiction and obsessive-compulsive disorders. A new study carried out by Lovinger and colleagues adds to the understanding of the brain circuits responsible for the habitual/goal-directed shift.

The results, published June 15 in Neuron, also point to a receptor called cannabinoid type 1 (CB1) as a key regulator of this circuitry.

The findings were made possible using a training strategy that enabled mice to push levers for food in both a habitual and goal-directed manner. The mice were placed in enclosures with differing visual decorations; the lever in the first dropped a food reward after it was pressed a certain number of times, while the lever in the second would drop a reward at a random time after the lever had been pressed once.

“In the first scenario, the mouse makes the connection quickly that pressing the lever 20 times, for example, gets it a reward,” Lovinger told Psychiatric News. “In the second enclosure, that contiguity is disrupted. The mouse knows that pressing will eventually lead to reward, but it doesn’t know how many, so it will just start pressing at a periodic rate.”

On alternate testing days, the mice were allowed to eat their treats prior to the testing, and on these days—termed the devalued state because the desire for the reward is lessened—mice pressed the lever far less in the goal-directed enclosure, but still roughly the same amount in the random-time enclosure—much like a habit.

The researchers then tried these tests out on mice in which the neurons that travel between the orbitofrontal cortex (OFC) and dorsal striatum (DS, which links decision making and reward behaviors) were blocked and observed that the mice kept pressing a lot in both enclosures, suggesting an inability to switch out of habit mode.

“Normally, on devalued days the urge to default to the habit of pressing the lever repeatedly gets suppressed in some way because the brain is providing information that the food isn’t as valuable,” Lovinger said.

With the OFC-DS connection identified, the next question was what part of these neurons was responsible for suppressing habits? Some previous work by Lovinger’s colleague and study coauthor Rui Costa, Ph.D., an investigator at the Champalimaud Institute for the Unknown in Lisbon, Portugal, pointed to CB1 as a potential candidate; the CB1 receptor interacts with endocannabinoids, natural messenger molecules in the body that are strikingly similar to THC, the active compound in marijuana.

When mice lacking the CB1 receptor in their OFC neurons were trained, they reduced their lever pressing in both enclosures on devalued days, reflective of a state in which the mice always used goal-directed behaviors because they could not form habits.

Having found CB1 as the receptor that Helps suppress habits, Lovinger said the next step would be to find the agent in the OFC-DS neural circuit that strengthens habits—and that should provide major clues about how drugs of abuse like alcohol and marijuana disrupt the normal process of habituation.

While the NIAAA is more focused on the addiction side, Lovinger thinks the current knowledge gained on weakened habits could be valuable in neuropsychiatry as well.

“It may be a bit of a stretch, but ADHD could be mediated in part by reduced habit-forming potential,” he said. “If someone is trying to pay attention to all potential outcomes in every decision, it could explain the lack of focus displayed by people with ADHD.””

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