Involvement of the opioid system in the anxiolytic-like effects induced by Delta(9)-tetrahydrocannabinol.

Recent studies have shown that several pharmacological actions induced by cannabinoids, including antinociception and reward, involve the participation of the endogenous opioid system. The present study was designed to examine the possible involvement of the different opioid receptors in the anxiolytic-like responses induced by Delta(9)-tetrahydrocannabinol (THC)…

The administration of a low dose of THC produced clear anxiolytic-like responses…

CONCLUSIONS:

These results demonstrate that the endogenous opioid system is involved in the regulation of anxiety-like behaviour by cannabinoids and provide new findings to clarify further the interaction between these two neuronal systems.”

http://www.ncbi.nlm.nih.gov/pubmed/12185408

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

Single-dose study of nabilone in anxious volunteers.

“The effects of single oral doses of nabilone, a synthetic cannabinoid, were studied in eight anxious volunteer subjects. Each subject had two exposures to placebo and three dose levels of nabilone at one-week intervals in a single-blind balanced Latin-square design after the nabilone dose range was determined by each subject’s response to a test dose. Heart rate and blood pressure were monitored. The Profile of Mood States (POMS), a self-rating adjective checklist, was used as the quantitative measure of subjective effects. Four subjects performed a continuous avoidance procedure. High doses (4 or 5 mg) of nabilone produced orthostatic hypotension in these subjects. Mild dose-related increases in heart rate also occurred. Despite the occurrence of highly significant levels of sedation, there were no significant effects of nabilone on the continuous avoidance procedure. Two of these four subjects experienced an antianxiety effect from low (1 or 2 mg) nabilone doses. Four other subjects received comparatively lower doses of nabilone and performed on three behavioral tasks at intervals before and after drug: a recognition memory procedure, a task requiring spaced responding at a controlled rate, and a reaction time task. In these subjects there were no reliable effects on blood pressure or heart rate, no significant subjective effects on the POMS, and no antianxiety effects. Drug effects were also minimal on the three behavioral tasks.”

http://www.ncbi.nlm.nih.gov/pubmed/6117576

Nabilone for the treatment of paraneoplastic night sweats: a report of four cases.

“Night sweats are one of many symptoms experienced by patients with advanced cancer. Persistent night sweats tend to decrease quality of life through interference with sleep… night sweats represent one of the symptoms that displays a tendency not to improve as patients with advanced cancer approach end of life…

This paper serves to report on the successful management of four patients suffering from persistent paraneoplastic night sweats using the synthetic orally administered cannabinoid nabilone…”

http://www.ncbi.nlm.nih.gov/pubmed/18715188

Inhibition of endocannabinoid catabolic enzymes elicits anxiolytic-like effects in the marble burying assay

“Cannabinoids have long been shown to have a range of potential therapeutic effects, including antiemetic actions, analgesia, and anxiolysis. These data indicate that elevation of AEA or 2-AG reduces marble burying behavior and suggest that their catabolic enzymes represent potential targets for the development of new classes of pharmacotherapeutics to treat anxiety-related disorders.

Marijuana is commonly smoked to reduce feelings of stress and anxiety… much interest has been generated by the discovery of the endogenous cannabinoid (i.e. endocannabinoid; eCB) system as a source of targets for the development of new therapeutic treatments of a range of ailments including anxiety and depression…”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3034086/

Anandamide hydrolysis: a new target for anti-anxiety drugs?

“The major psychoactive constituent of cannabis, Delta(9)-tetrahydrocannabinol, affects emotional states in humans and laboratory animals by activating brain cannabinoid receptors. A primary endogenous ligand of these receptors is anandamide, the amide of arachidonic acid with ethanolamine. Anandamide is released in selected regions of the brain and is deactivated through a two-step process consisting of transport into cells followed by intracellular hydrolysis. Pharmacological blockade of the enzyme fatty acid amide hydrolase (FAAH), which is responsible for intracellular anandamide degradation, produces anxiolytic-like effects in rats without causing the wide spectrum of behavioral responses typical of direct-acting cannabinoid agonists. These findings suggest that anandamide contributes to the regulation of emotion and anxiety, and that FAAH might be the target for a novel class of anxiolytic drugs.”

http://www.ncbi.nlm.nih.gov/pubmed/14604824

Interaction between cannabinoid compounds and diazepam on anxiety-like behaviour of mice.

“Previous studies have suggested that cannabinoidergic system is involved in anxiety. However, a complete picture of cannabinoid association in the anxiety is still lacking. In the present study, we investigated the possible interaction between cannabinoidergic and GABAergic systems in the anxiety-like behaviour of mice…

 Taken together, the present study showed that co-administration of exogenous cannabinoids and diazepam produce additive or synergistic effect at different combinations. Moreover, it has been shown that enhancement of the function of endocannabinoids could increase the anxiolytic effect of diazepam.”

http://www.ncbi.nlm.nih.gov/pubmed/18096213

Cannabinoid CB1 receptors of the rat central amygdala mediate anxiety-like behavior: interaction with the opioid system.

“Cannabinoids, which are the active compounds of marijuana, produce some pharmacological effects similar to the opioids. In addition, there are functional interactions between the cannabinoid and opioid systems. In this study, we investigated the effects of intraperitoneal (i.p.) injection of opioid drugs on responses induced by intracentral amygdala (intra-CeA) microinjection of cannabinoid CB1 receptor agents in rats, using the elevated plus maze test of anxiety…

 In conclusion, the results may indicate an anxiolytic-like effect for cannabinoid CB1 receptors of the CeA and the existence of an interaction between the cannabinoid and the opioid systems in the modulation of anxiety.” 

http://www.ncbi.nlm.nih.gov/pubmed/18797248

Activation of cannabinoid CB1 receptors in the dorsolateral periaqueductal gray induces anxiolytic effects in rats submitted to the Vogel conflict test.

“Activation of cannabinoid CB(1) receptors in the dorsolateral periaqueductal gray induces anxiolytic-like effects in the elevated plus maze. The aim of this work was to verify if facilitation of endocannabinoid-mediated neurotransmission in this region would also produce anxiolytic-like effects in another model of anxiety, the Vogel conflict test…

The results give further support to the proposal that facilitation of CB(1) receptor-mediated endocannabinoid neurotransmission in the dorsolateral periaqueductal gray modulates defensive responses.”

http://www.ncbi.nlm.nih.gov/pubmed/18691568