“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.”
Tag Archives: Cannabinoids
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.”
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…”
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.”
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.”
CB1 cannabinoid receptors mediate anxiolytic effects: convergent genetic and pharmacological evidence with CB1-specific agents.
“Cannabinoids are known to modulate GABAergic and glutamatergic transmission in cortical areas, the former via CB1 and the latter via a novel receptor. Pharmacological data demonstrate that several widely used cannabinoid ligands bind to both receptors, which may explain the inconsistencies in their behavioural effects.
In the present experiments, we studied the effects of the CB1 antagonist… and the cannabinoid agonist… in wild-type as well as in CB1 knockout mice… In wild types, the cannabinoid agonist… caused a decrease in anxiety-like behaviour, which was abolished by the CB1-selective antagonist…
Our studies on the behavioural effects of the cannabinoid antagonist SR-141716A and the CB1 antagonist AM-251 show that the CB1 and the novel cannabinoid receptor mediate anxiolytic (anti-anxiety) and anxiogenic (anxiety) effects, respectively.
This suggests that agonists of the former, or antagonists of the latter, are promising new compounds in the pharmacotherapy of anxiety.”
Anti-Aversive Effects of Cannabidiol on Innate Fear-Induced Behaviors Evoked by an Ethological Model of Panic Attacks Based on a Prey vs the Wild Snake Epicrates cenchria crassus Confrontation Paradigm
“Research on the interaction between different compounds extracted from the plant Cannabis sativa (Cannabis) and the endocannabinoid system has revealed a series of ligands that selectively bind to cannabinoid receptors. The activation of this system causes a wide spectrum of responses, some of which could be potentially therapeutic. Recently, much attention has been given to cannabidiol (CBD), a major constituent of Cannabis that is unable to mimic all of the effects of the plant but has a wide range of pharmacological effects. In the elevated plus-maze, this drug produces an anxiolytic-like effect…
… attention has been given to the potential anxiolytic properties of cannabidiol, because of its complex actions on the endocannabinoid system together with its effects on other neurotransmitter systems. The aim of this study was to investigate the effects of cannabidiol on innate fear-related behaviors evoked by a prey vs predator paradigm…
These results show that cannabidiol modulates defensive behaviors evoked by the presence of threatening stimuli…
In summary, the data presented in this study suggest that the complex action of CBD on the endocannabinoid-mediated system, together with its putative effect on the serotonin-mediated system, could have a pivotal role in the regulation of emotional states and thus constitute a novel pharmacological target for anti-panic therapy.”
Mitigation of post-traumatic stress symptoms by Cannabis resin: a review of the clinical and neurobiological evidence.
“It is known from clinical studies that some patients attempt to cope with the symptoms of post-traumatic stress disorder (PTSD) by using recreational drugs. This review presents a case report of a 19-year-old male patient with a spectrum of severe PTSD symptoms, such as intense flashbacks, panic attacks, and self-mutilation, who discovered that some of his major symptoms were dramatically reduced by smoking cannabis resin. The major part of this review is concerned with the clinical and preclinical neurobiological evidence in order to offer a potential explanation of these effects on symptom reduction in PTSD.
This review shows that recent studies provided supporting evidence that PTSD patients may be able to cope with their symptoms by using cannabis products. Cannabis may dampen the strength or emotional impact of traumatic memories through synergistic mechanisms that might make it easier for people with PTSD to rest or sleep and to feel less anxious and less involved with flashback memories.
The presence of endocannabinoid signalling systems within stress-sensitive nuclei of the hypothalamus, as well as upstream limbic structures (amygdala), point to the significance of this system for the regulation of neuroendocrine and behavioural responses to stress.
Evidence is increasingly accumulating that cannabinoids might play a role in fear extinction and antidepressive effects. It is concluded that further studies are warranted in order to evaluate the therapeutic potential of cannabinoids in PTSD.”
Endocannabinoid system dysfunction in mood and related disorders.
“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.”
Endocannabinoid system and mood disorders: Priming a target for new therapies.
“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.”