Effects of delta9-tetrahydrocannabinol on reward and anxiety in rats exposed to chronic unpredictable stress.

“The aim of this study was to examine how exposure to chronic unpredictable stress (CUS) will affect reward function and anxiety after acute administration of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) in rats…

…both the low and the high dose of Delta(9)-THC exerted anxiolytic-like effects…

The present results provide clear evidence for an anxiolytic effect of Delta(9)-THC both in stressed and in nonstressed animals…”

http://www.ncbi.nlm.nih.gov/pubmed/19406854

Impaired action of anxiolytic drugs in mice deficient in cannabinoid CB1 receptors.

“The role of cannabinoid CB(1) receptors in the action of anxiolytics was examined. Deletion of CB(1) receptors resulted in increased anxiety-like behaviours… Our findings reveal that CB(1) receptors are involved in the regulation of emotional responses, and play a pivotal role in the action mechanism of anxiolytics. They suggest that alterations in the functional activity of the CB(1) receptor may be related to the emergence of anxiety disorders, and may affect treatment with anxiolytics.”

http://www.ncbi.nlm.nih.gov/pubmed/15081793

[Benefits of an add-on treatment with the synthetic cannabinomimetic nabilone on patients with chronic pain–a randomized controlled trial].

“The aim of this study was to investigate the efficacy and efficiency of an add-on treatment with the synthetic cannabinomimetic nabilone on patients with chronic pain. Of major interest were the evaluation of the influence the treatment had on pain and on quality of life as well as the subjective assessment of positive effects and side effects by the study participants…

CONCLUSION:

In summary, the study results allow the conclusion that a majority of patients with chronic pain classify nabilone intake in addition to the standard treatment as a measure with a positive individual benefit-riskratio. Thus, this kind of treatment may be an interesting and attractive enrichment of analgetic therapy concepts.”

http://www.ncbi.nlm.nih.gov/pubmed/16855921

Randomised, double-blind, placebo-controlled trial to assess the potential of cannabinoid receptor stimulation in the treatment of dystonia.

“Cannabis may have medicinal uses in a variety of diseases. The neural mechanisms underlying dystonia involve abnormalities within the basal ganglia-in particular, overactivity of the lateral globus pallidus (GPl). Cannabinoid receptors are located presynaptically on GABA terminals within the GPi, where their activation reduces GABA reuptake. Cannabinoid receptor stimulation may thus reduce overactivity of the GPl and thereby reduce dystonia. A double-blind, randomised, placebo-controlled, crossover study using the synthetic cannabinoid receptor agonist nabilone in patients with generalised and segmental primary dystonia showed no significant reduction in dystonia following treatment with nabilone.”

http://www.ncbi.nlm.nih.gov/pubmed/11835452

The efficacy and safety of nabilone (a synthetic cannabinoid) in the treatment of anxiety.

“The anxiolytic properties of nabilone, a synthetic cannabinoid resembling the natural cannabinoids, were studied in 25 outpatients suffering from anxiety. The drug was compared with a placebo in a double-blind manner over a 28-day treatment period. Patients were seen weekly by the physician and were rated by the Hamilton Rating Scale for Anxiety and the Patient’s Global Evaluation as well as by patient-rated evaluations. The results of the study showed a dramatic improvement in anxiety in the nabilone group when compared with placebo (P less than 0.001). Side effects reported were dry mouth, dry eyes, and drowsiness. Patients did not report any of the subjective “altered state” experience of marihuana.”

http://www.ncbi.nlm.nih.gov/pubmed/6117575

Experience with the synthetic cannabinoid nabilone in chronic noncancer pain.

“Chronic noncancer pain includes a heterogeneous group of disorders and is often refractory to treatment. Cannabis products have historically been used for chronic pain and are attracting renewed pharmaceutical interest. Nabilone is a synthetic cannabinoid licensed in Canada for the treatment of severe nausea and vomiting associated with cancer chemotherapy. We have used nabilone off-label for the treatment of chronic noncancer pain since 1999. In this article, we review our clinical experience of 20 adult patients with chronic noncancer pain who had been treated with nabilone and followed up for an average of 1.5 years. Prior to nabilone therapy, patients had used a wide range of therapies, including 11 who had used cannabis. Fifteen patients reported subjective overall improvement with nabilone, and nine reported reduced pain intensity. Beneficial effects on sleep and nausea were the main reasons for continuing use. Intolerable side effects were experienced in three patients (palpitations, urinary retention, dry mouth). Nabilone may be a useful addition to pain management and should be further evaluated in randomized controlled trials.”

http://www.ncbi.nlm.nih.gov/pubmed/16533193

The cannabinoid CB1 receptor is involved in the anxiolytic, sedative and amnesic actions of benzodiazepines.

“Previous studies in our laboratory showed that cannabinoid CB1 receptor knockout mice (CB1-/-) presented increased anxiety-like behaviours that did not respond to the anxiolytic actions of benzodiazepines. These results suggest that the pharmacological effects of benzodiazepines may involve the participation of cannabinoid CB1 receptors. Therefore, the purpose of this study was to examine the effects of alprazolam and the cannabinoid CB1 receptor antagonist…

Taken together, these findings revealed that cannabinoid CB1 receptor plays a pivotal role in the pharmacological actions of benzodiazepines. Furthermore, these results suggest that blockade of cannabinoid CB1 receptors may be useful in the treatment of patients with problems related to the consumption of benzodiazepines. Further clinical trials are needed to test this hypothesis.”

http://www.ncbi.nlm.nih.gov/pubmed/19825899

Cannabinoid-1 receptor: a novel target for the treatment of neuropsychiatric disorders.

“G-protein-coupled receptor (GPCR)-mediated signalling is the most widely used signalling mechanism in cells, and its regulation is important for various physiological functions. The cannabinoid-1 (CB(1)) receptor, a GPCR, has been shown to play a critical role in neural circuitries mediating motivation, mood and emotional behaviours.

 Several recent studies have indicated that impairment of CB(1) receptor-mediated signalling may play a critical role in the pathophysiology of various neuropsychiatric disorders. In this article, the authors briefly review literature relating to the role played by the endocannabinoid system in various neuropsychiatric disorders, and the CB(1) receptor as a potential therapeutic target for the treatment of alcoholism, depression, anxiety and schizophrenia.”

http://www.ncbi.nlm.nih.gov/pubmed/16548770

5-HT1A receptors are involved in the cannabidiol-induced attenuation of behavioural and cardiovascular responses to acute restraint stress in rats.

“Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa which induces anxiolytic- and antipsychotic-like effects in rodents. These effects could be mediated by facilitation of the endocannabinoid system or by the activation of 5-HT(1A) receptors. As either of these mechanisms could promote adaptation to inescapable stress, the aim of the present work was to test the hypothesis that CBD would attenuate the autonomic and behavioural consequences of restraint stress (RS). We also investigated if the responses to CBD depended on activation of 5-HT(1A) receptors.

Cannabidiol (CBD)… cannabinoid generally found in relatively high concentrations in cannabis, exhibits a somewhat different pharmacology compared with THC. CBD attenuates the psychotomimetic and anxiogenic effects of THC in humans.

 Moreover, systemic administration of CBD induced antipsychotic and anxiolytic-like effects…

CONCLUSION AND IMPLICATIONS:

The results suggest that CBD can attenuate acute autonomic responses to stress and its delayed emotional consequences by facilitating 5-HT(1A) receptor-mediated neurotransmission.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697769/

 

Cannabidiol blocks long-lasting behavioral consequences of predator threat stress: possible involvement of 5HT1A receptors.

“Posttraumatic stress disorder (PTSD) is an incapacitating syndrome that follows a traumatic experience. Predator exposure promotes long-lasting anxiogenic effect in rodents, an effect related to symptoms found in PTSD patients. Cannabidiol (CBD) is a non-psychotomimetic component of Cannabis sativa with anxiolytic effects. The present study investigated the anti-anxiety actions of CBD administration in a model of PTSD…

 Repeated administration of CBD prevented long-lasting anxiogenic effects promoted by a single predator exposure…

 In conclusion, predator exposure promotes long-lasting up-regulation of 5HT1A receptor gene expression in the hippocampus and frontal cortex. Repeated CBD administration prevents the long-lasting anxiogenic effects observed after predator exposure probably by facilitating 5HT1A receptors neurotransmission.

Our results suggest that CBD has beneficial potential for PTSD treatment and that 5HT1A receptors could be a therapeutic target in this disorder.”

http://www.ncbi.nlm.nih.gov/pubmed/22979992