Antipsychotic profile of cannabidiol and rimonabant in an animal model of emotional context processing in schizophrenia.

“Clinical and neurobiological findings suggest that cannabinoids and their receptors are implicated in schizophrenia. Cannabidiol (CBD), a non-psychotomimetic compound of the Cannabis sativa plant, has been reported to have central therapeutic actions, such as antipsychotic and anxiolytic effects…

Our results suggest a potential therapeutical effect of CBD and rimonabant to treat the emotional processing impairment presented in schizophrenia.

In addition, our results reinforce the anxiolytic profile of CBD.”

http://www.ncbi.nlm.nih.gov/pubmed/22716146

Cannabidiol in Humans-The Quest for Therapeutic Targets.

“Cannabidiol (CBD), a major phytocannabinoid constituent of cannabis, is attracting growing attention in medicine for its anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties.

However, up to this point, a comprehensive literature review of the effects of CBD in humans is lacking. The aim of the present systematic review is to examine the randomized and crossover studies that administered CBD to healthy controls and to clinical patients.

A systematic search was performed in the electronic databases PubMed and EMBASE using the key word “cannabidiol”. Both monotherapy and combination studies (e.g., CBD + ∆9-THC) were included. A total of 34 studies were identified: 16 of these were experimental studies, conducted in healthy subjects, and 18 were conducted in clinical populations, including multiple sclerosis (six studies), schizophrenia and bipolar mania (four studies), social anxiety disorder (two studies), neuropathic and cancer pain (two studies), cancer anorexia (one study), Huntington’s disease (one study), insomnia (one study), and epilepsy (one study).

Experimental studies indicate that a high-dose of inhaled/intravenous CBD is required to inhibit the effects of a lower dose of ∆9-THC. Moreover, some experimental and clinical studies suggest that oral/oromucosal CBD may prolong and/or intensify ∆9-THC-induced effects, whereas others suggest that it may inhibit ∆9-THC-induced effects.

Finally, preliminary clinical trials suggest that high-dose oral CBD  may exert a therapeutic effect for social anxiety disorder, insomnia and epilepsy, but also that it may cause mental sedation. Potential pharmacokinetic and pharmacodynamic explanations for these results are discussed.”

http://www.ncbi.nlm.nih.gov/pubmed/24281562

Memory-rescuing effects of cannabidiol in an animal model of cognitive impairment relevant to neurodegenerative disorders.

“Cannabidiol, the main nonpsychotropic constituent of Cannabis sativa, possesses a large number of pharmacological effects including anticonvulsive, sedative, hypnotic, anxiolytic, antipsychotic, anti-inflammatory, and neuroprotective, as demonstrated in clinical and preclinical studies.

 Many neurodegenerative disorders involve cognitive deficits, and this has led to interest in whether cannabidiol could be useful in the treatment of memory impairment associated to these diseases…

We used an animal model of cognitive impairment induced by iron overload in order to test the effects of cannabidiol in memory-impaired rats…

RESULTS:

A single acute injection of cannabidiol at the highest dose was able to recover memory in iron-treated rats. Chronic cannabidiol improved recognition memory in iron-treated rats. Acute or chronic cannabidiol does not affect memory in control rats.

CONCLUSIONS:

The present findings provide evidence suggesting the potential use of cannabidiol for the treatment of cognitive decline associated with neurodegenerative disorders.

 Further studies, including clinical trials, are warranted to determine the usefulness of cannabidiol in humans suffering from neurodegenerative disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/21870037

Cannabis by product helps reduce effects of Parkinson disease medication

“Researchers from Brazil’s prestigious University of Sao Paulo have discovered that marihuana contains substances which can help ease the collateral effects of medicines prescribed to patients suffering from Parkinson disease.”

Brazilian researchers have tested the positive effects of canabiodiol 

“Six patients with Parkinson were given during a whole month small doses of “canabiodiol” one of the 400 substances in marihuana, following which encouraging results were confirmed according to scientists from the Riberao Preto Medicine School from the SP University.

“Patients with Parkinson developed improvements in their sleeping alterations, in their psychotic symptoms and could even reduce their trembling” said psychiatrist Jose Alexander Crippa, Neuro-sciences Department professor.

The paper on the discovery was published last November and next year an additional paper with test results on the anxiolytic effects of “canabiodiol” in patients with obsession and compulsion disorders will be released.

A group of voluntary patients with obsessive and compulsive conducts were medicated with the substance 70 minutes before facing situations that forced them into anxiety fits, and “improvements were evident”.”

http://en.mercopress.com/2009/12/30/cannabis-by-product-helps-reduce-effects-of-parkinson-disease-medication

The endocannabinoid system in anxiety, fear memory and habituation.

“Evidence for the involvement of the endocannabinoid system (ECS) in anxiety and fear has been accumulated, providing leads for novel therapeutic approaches. In anxiety, a bidirectional influence of the ECS has been reported, whereby anxiolytic and anxiogenic responses have been obtained after both increases and decreases of the endocannabinoid tone. The recently developed genetic tools have revealed different but complementary roles for the cannabinoid type 1 (CB1) receptor on GABAergic and glutamatergic neuronal populations. This dual functionality, together with the plasticity of CB1 receptor expression, particularly on GABAergic neurons, as induced by stressful and rewarding experiences, gives the ECS a unique regulatory capacity for maintaining emotional homeostasis. However, the promiscuity of the endogenous ligands of the CB1 receptor complicates the interpretation of experimental data concerning ECS and anxiety. In fear memory paradigms, the ECS is mostly involved in the two opposing processes of reconsolidation and extinction of the fear memory. Whereas ECS activation deteriorates reconsolidation, proper extinction depends on intact CB1 receptor signalling. Thus, both for anxiety and fear memory processing, endocannabinoid signalling may ensure an appropriate reaction to stressful events. Therefore, the ECS can be considered as a regulatory buffer system for emotional responses.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3267552/

Endocannabinoids mediate anxiolytic-like effect of acetaminophen via CB1 receptors.

“Acetaminophen (Paracetamol), a most commonly used antipyretic/analgesic agent, is metabolized to AM404 (N-arachidonoylphenolamine) that inhibits uptake and degradation of anandamide which is reported to mediate the analgesic action of acetaminophen via CB1 receptor. AM404 and anandamide are also reported to produce anxiolytic-like behavior. In view of the implication of endocannabinoids in the effect of acetaminophen, we contemplated that acetaminophen may have anxiolytic-like effect. Therefore, this possibility was tested by observing the effects of various doses of acetaminophen in mice on anxiety-related indices of Vogel conflict test and social interaction test. The results from both the tests indicated that acetaminophen (50, 100, or 200 mg/kg, i.p.) or anandamide (10 or 20 microg/mouse, i.c.v.) dose dependently elicited anxiolytic-like effect, that was comparable to diazepam (2 mg/kg, i.p.). Moreover, co-administration of sub-effective dose of acetaminophen (25 mg/kg, i.p.) and anandamide (5 microg/mouse, i.c.v) produced similar anxiolytic effect. Further, pre-treatment with AM251 (a CB1 receptor antagonist; 1 mg/kg, i.p.) antagonized the effects of acetaminophen and anandamide with no per se effect at 1 mg/kg dose, while anxiogenic effect was evident at a higher dose (5 mg/kg, i.p.). None of the treatment/s was found to induce any antinociceptive or locomotor impairment effects. In conclusion, the findings suggested that acetaminophen (50, 100, or 200 mg/kg, i.p.) exhibited dose dependent anxiolytic effect in mice and probably involved endocannabinoid-mediated mechanism in its effect.”

http://www.ncbi.nlm.nih.gov/pubmed/19580839

Pot Compound Reduces Anxiety

“According to clinical trial data published online in The Journal of Psychopharmacology, the administration of the non-psychoactive component of marijuana [cannabinoid cannabidiol (CBD)] reduces anxiety in subjects with social anxiety disorder (SAD).

The anti-anxiety activity of oral doses of CBD in ten subjects was assessed by investigators at the University of Sao Paulo in Brazil in a double blind, placebo-controlled trial.

Researchers concluded, “CBD reduces anxiety in SAD and that this is related to its effects on activity in limbic and paralimbic brain areas.”

This study is the first clinical trial to investigate the effects of cannabinoid cannabidiol on human pathological anxiety and its underlying brain mechanisms.

Previous studies in the context of CBD have suggested that the compound possesses anti-inflammatory activity, anti-cancer activity, and neuroprotective effects – among other therapeutic properties.

The study “Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report,” appeared online in The Journal of Psychopharmacology.”

http://www.imarijuana.com/news/pot-compound-reduces-anxiety

Antianxiety effect of cannabidiol in the elevated plus-maze.

“In order to assess the presence of anxiolytic properties in cannabidiol (CBD) the drug was tested in an elevated plus-maze model of anxiety, in rats. Doses of 2.5, 5.0 and 10.0 mg/kg significantly increased the entry ratio (open/total number of entries), an anxiolytic-like effect. CBD at a dose of 20.0 mg/kg was no longer effective. None of the doses of CBD used changed total number of entries, a measure of total exploratory activity. Diazepam (2.0 mg/kg) also caused an anxiolytic-like effect in this model.

These results indicate that CBD causes a selective anxiolytic effect in the elevated plus-maze, within a limited range of doses.”

http://www.ncbi.nlm.nih.gov/pubmed/1969666

Effects of Cannabidiol (CBD) on Regional Cerebral Blood Flow

“Animal and human studies have suggested that cannabidiol (CBD) may possess anxiolytic properties…These results suggest that CBD has anxiolytic properties, and that these effects are mediated by an action on limbic and paralimbic brain areas…

Cannabidiol (CBD) constitutes up to 40% of Cannabis sativa and has quite different psychological effects to the plant’s best known constituent, Delta9-tetrahydrocannabinol (Delta9-THC)

 In particular, in animal studies CBD has effects similar to anxiolytic drugs…”

 http://www.nature.com/npp/journal/v29/n2/full/1300340a.html

Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report.

“Animal and human studies indicate that cannabidiol (CBD), a major constituent of cannabis, has anxiolytic properties. However, no study to date has investigated the effects of this compound on human pathological anxiety and its underlying brain mechanisms. The aim of the present study was to investigate this in patients with generalized social anxiety disorder (SAD) using functional neuroimaging. Regional cerebral blood flow (rCBF) at rest was measured twice using (99m)Tc-ECD SPECT in 10 treatment-naïve patients with SAD. In the first session, subjects were given an oral dose of CBD (400 mg) or placebo, in a double-blind procedure. In the second session, the same procedure was performed using the drug that had not been administered in the previous session. Within-subject between-condition rCBF comparisons were performed using statistical parametric mapping. Relative to placebo, CBD was associated with significantly decreased subjective anxiety (p < 0.001), reduced ECD uptake in the left parahippocampal gyrus, hippocampus, and inferior temporal gyrus (p < 0.001, uncorrected), and increased ECD uptake in the right posterior cingulate gyrus (p < 0.001, uncorrected).

These results suggest that CBD reduces anxiety in SAD and that this is related to its effects on activity in limbic and paralimbic brain areas.”

http://www.ncbi.nlm.nih.gov/pubmed/20829306