Tag Archives: THC

Adjunctive nabilone in cancer pain and symptom management: a prospective observational study using propensity scoring.

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“A prospective observational study assessed the effectiveness of adjuvant nabilone (Cesamet) therapy in managing pain and symptoms experienced by advanced cancer patients… When compared with those not taking nabilone, patients using this cannabinoid had a lower rate of starting nonsteroidal anti-inflammatory agents, tricyclic antidepressants, gabapentin, dexamethasone, metoclopramide, and ondansetron and a greater tendency to discontinue these drugs.”

http://www.ncbi.nlm.nih.gov/pubmed/18402303

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

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“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

Single-dose study of nabilone in anxious volunteers.

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“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

Experience with the synthetic cannabinoid nabilone in chronic noncancer pain.

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“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

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

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“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

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

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“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

A role for cannabinoid CB1 receptors in mood and anxiety disorders.

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“Mood and anxiety disorders, the most prevalent of the psychiatric disorders, cause immeasurable suffering worldwide. Despite impressive advances in pharmacological therapies, improvements in efficacy and side-effect profiles are needed. The present literature review examines the role that the endocannabinoid system may play in these disorders and the potential value of targeting this system in the search for novel and improved medications.

Cannabis and its major psychoactive component (-)-trans-delta9-tetrahydrocannabinol, have profound effects on mood and can modulate anxiety and mood states. Cannabinoid receptors and other protein targets in the central nervous system (CNS) that modulate endocannabinoid function have been described. The discovery of selective modulators of some of these sites that increase or decrease endocannabinoid neurotransmission, primarily through the most prominent of the cannabinoid receptors in the CNS, the CB1 receptors, combined with transgenic mouse technology, has enabled detailed investigations into the role of these CNS sites in the regulation of mood and anxiety states. Although data point to the involvement of the endocannabinoid system in anxiety states, the pharmacological evidence seems contradictory: both anxiolytic- and anxiogenic-like effects have been reported with both endocannabinoid neurotransmission enhancers and blockers.

Due to advances in the development of selective compounds directed at the CB1 receptors, significant progress has been made on this target. Recent biochemical and behavioural findings have demonstrated that blockade of CB1 receptors engenders antidepressant-like neurochemical changes (increases in extracellular levels of monoamines in cortical but not subcortical brain regions) and behavioural effects consistent with antidepressant/antistress activity in rodents.”

http://www.ncbi.nlm.nih.gov/pubmed/16148437

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

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“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/

 

Endocannabinoid system dysfunction in mood and related disorders.

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“The endocannabinoid (EC) system is widely distributed throughout the brain and modulates many functions. It is involved in mood and related disorders, and its activity may be modified by exogenous cannabinoids. This article examines the therapeutic potential of cannabinoids in psychiatric disorders.

We propose (hypothesize) that the EC system, which is homoeostatic in cortical excitation and inhibition, is dysfunctional in mood and related disorders. Anandamide, tetrahydrocannabinol (THC) and cannabidiol (CBD) variously combine antidepressant, antipsychotic, anxiolytic, analgesic, anticonvulsant actions, suggesting a therapeutic potential in mood and related disorders. Currently, cannabinoids find a role in pain control. Post mortem and other studies report EC system abnormalities in depression, schizophrenia and suicide. Abnormalities in the cannabinoid-1 receptor (CNR1) gene that codes for cannabinoid-1 (CB1) receptors are reported in psychiatric disorders. However, efficacy trials of cannabinoids in psychiatric disorders are limited but offer some encouragement.

CONCLUSION:

Research is needed to elucidate the role of the EC system in psychiatric disorders and for clinical trials with THC, CBD and synthetic cannabinoids to assess their therapeutic potential.”

http://www.ncbi.nlm.nih.gov/pubmed/21916860

Endocannabinoid system and mood disorders: Priming a target for new therapies.

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“The endocannabinoid system (ECS), comprising two G protein-coupled receptors (the cannabinoid receptors 1 and 2 [CB1 and CB2] for marijuana’s psychoactive principle ∆(9)-tetrahydrocannabinol [∆(9)-THC]), their endogenous small lipid ligands (namely anandamide [AEA] and 2-arachidonoylglycerol [2-AG], also known as endocannabinoids), and the proteins for endocannabinoid biosynthesis and degradation, has been suggested as a pro-homeostatic and pleiotropic signaling system activated in a time- and tissue-specific way during physiopathological conditions. In the brain activation of this system modulates the release of excitatory and inhibitory neurotransmitters and of cytokines from glial cells. As such, the ECS is strongly involved in neuropsychiatric disorders, particularly in affective disturbances such as anxiety and depression. It has been proposed that synthetic molecules that inhibit endocannabinoid degradation can exploit the selectivity of endocannabinoid action, thus activating cannabinoid receptors only in those tissues where there is perturbed endocannabinoid turnover due to the disorder, and avoiding the potential side effects of direct CB1 and CB2 activation. However, the realization that endocannabinoids, and AEA in particular, also act at other molecular targets, and that these mediators can be deactivated by redundant pathways, has recently led to question the efficacy of such approach, thus opening the way to new multi-target therapeutic strategies, and to the use of non-psychotropic cannabinoids, such as cannabidiol (CBD), which act via several parallel mechanisms, including indirect interactions with the ECS. The state of the art of the possible therapeutic use of endocannabinoid deactivation inhibitors and phytocannabinoids in mood disorders is discussed in this review article.”

http://www.ncbi.nlm.nih.gov/pubmed/23261685