A safer alternative: Cannabis substitution as harm reduction.

“Harm reduction is a set of strategies that aim to minimise problems associated with drug use while recognising that for some users, abstinence may be neither a realistic nor a desirable goal.

In this paper, we aim for deeper understandings of older adult cannabis users’ beliefs and substitution practices as part of the harm reduction framework..

Study participants described using cannabis as a safer alternative for alcohol, illicit drugs and pharmaceuticals based on their perceptions of less adverse side effects, low-risk for addiction and greater effectiveness at relieving symptoms, such as chronic pain.

Cannabis substitution can be an effective harm reduction method for those who are unable or unwilling to stop using drugs completely.”

http://www.ncbi.nlm.nih.gov/pubmed/25919477

http://www.thctotalhealthcare.com/category/addiction/

 

Role of CB2 receptors in social and aggressive behavior in male mice.

“This study was designed to examine the role of cannabinoid CB2r in social and aggressive behavior…

Our results suggest that CB2r is implicated in social interaction and aggressive behavior and deserves further consideration as a potential new target for the management of aggression.”

http://www.ncbi.nlm.nih.gov/pubmed/25921034

Endocannabinoids regulate the activity of astrocytic hemichannels and the microglial response against an injury: In vivo studies.

“Anandamide (AEA) is an endocannabinoid (EC) that modulates multiple functions in the CNS and that is released in areas of injury, exerting putative neuroprotective actions.

In the present study, we have used intravital microscopy to analyze the role of the EC system in the glial response against an acute insult…

In summary, these findings demonstrate that AEA modifies glial functions by promoting an enhanced pro-inflammatory glial response in the brain.”

http://www.ncbi.nlm.nih.gov/pubmed/25917763

Alkylindole-sensitive receptors modulate microglial cell migration and proliferation.

“Ligands targeting G protein-coupled receptors (GPCR) expressed by microglia have been shown to regulate distinct components of their activation process, including cell proliferation, migration and differentiation into M1 or M2 phenotypes.

Cannabinoids, including the active component of the Cannabis plant, tetrahydrocannabinol (THC), and the synthetic alkylindole (AI) compound, WIN55212-2 (WIN-2), activate two molecularly identified GPCRs: CB1 and CB2 .

Our results suggest that microglia express functional AI-sensitive receptors that control select components of their activation process.

Agonists of these novel targets might represent a novel class of therapeutics to influence the microglial cell activation process. ”

http://www.ncbi.nlm.nih.gov/pubmed/25914169

The monoacylglycerol lipase inhibitor JZL184 decreases inflammatory response in skeletal muscle contusion in rats.

“Muscle wound healing process is a typical inflammation-evoked event. The monoacylglycerol lipase (MAGL) inhibitor (4-nitrophenyl)4-[bis(1,3-benzodioxol -5-yl)-hydroxymethyl]piperidine-1-carboxylate (JZL184) has been previously reported to reduce inflammation in colitis and acute lung injury in mice, which provide a new strategy for primary care of skeletal muscle injury.

Our findings demonstrate that JZL184 is able to inhibit the inflammatory response and interfere with contused muscle healing, in which the anti-inflammatory action may be mediated through cannabinoid CB1 and CB2 receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/25912803

Distinct roles of the endocannabinoids anandamide and 2-arachidonoylglycerol in social behavior and emotionality at different developmental ages in rats.

“To date, our understanding of the relative contribution and potential overlapping roles of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in the regulation of brain function and behavior is still limited. To address this issue, we investigated the effects of systemic administration of JZL195, that simultaneously increases AEA and 2-AG signaling by inhibiting their hydrolysis, in the regulation of socio-emotional behavior in adolescent and adult rats.

These findings provide the first evidence for a role of 2-AG in social behavior, highlight the different contributions of AEA and 2-AG in the modulation of emotionality at different developmental ages and suggest that pharmacological inhibition of AEA and 2-AG hydrolysis is a useful approach to investigate the role of these endocannabinoids in neurobehavioral processes.”

http://www.ncbi.nlm.nih.gov/pubmed/25914159

Cannabidiol in medicine: a review of its therapeutic potential in CNS disorders.

“Cannabidiol (CBD) is the main non-psychotropic component of the glandular hairs of Cannabis sativa.

It displays a plethora of actions including anticonvulsive, sedative, hypnotic, antipsychotic, antiinflammatory and neuroprotective properties.

However, it is well established that CBD produces its biological effects without exerting significant intrinsic activity upon cannabinoid receptors.

For this reason, CBD lacks the unwanted psychotropic effects characteristic of marijuana derivatives, so representing one of the bioactive constituents of Cannabis sativa with the highest potential for therapeutic use.

The present review reports the pharmacological profile of CBD and summarizes results from preclinical and clinical studies utilizing CBD, alone or in combination with other phytocannabinoids, for the treatment of a number of CNS disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/18844286

Responsible and controlled use: Older cannabis users and harm reduction.

“Cannabis use is becoming more accepted in mainstream society. In this paper, we use Zinberg’s classic theoretical framework of drug, set, and setting to elucidate how older adult cannabis users managed health, social and legal risks in a context of normalized cannabis use…

Interviewees made harm reduction choices based on preferred cannabis derivatives and routes of administration, as well as why, when, where, and with whom to use. Most interviewees minimized cannabis-related harms so they could maintain social functioning in their everyday lives. Responsible and controlled use was described as moderation of quantity and frequency of cannabis used, using in appropriate settings, and respect for non-users. Users contributed to the normalization of cannabis use through normification.

Participants followed rituals or cultural practices, characterized by sanctions that helped define “normal” or “acceptable” cannabis use. Users contributed to cannabis normalization through their harm reduction methods.

These cultural practices may prove to be more effective than formal legal prohibitions in reducing cannabis-related harms.

Findings also suggest that users with access to a regulated market (medical cannabis dispensaries) were better equipped to practice harm reduction.

More research is needed on both cannabis culture and alternative routes of administration as harm reduction methods.”

http://www.ncbi.nlm.nih.gov/pubmed/25911027

The complex modulation of lysosomal degradation pathways by cannabinoid receptor 1 and 2.

“The two main receptors of the endocannabinoid system, cannabinoid receptor 1 (CB1R) and 2 (CB2R) were described in the early 1990s. Since then, different physiological functions have been revealed that are linked to the activity of these two G-protein-coupled receptors.

CB1R and CB2R activity influences signal Cascades, which are known to play a role in the regulation of the cellular “self-digestion” process called autophagy. A variety of these signaling pathways are integrated by the mammalian target of rapamycin complex 1 (mTORC1) that acts as an inhibitor of autophagy. Others, like AMP-activated protein kinase dependent signaling pathway, are able to bypass mTORC1 to modulate the autophagic activity directly.

In the recent years, several scientific reports demonstrate an involvement of CB1R and CB2R signaling in the control of the autophagic activity in different paradigms.

In this review, we summarize the recent literature on this topic, which is in part contradictory and therefore, it is of great importance to illuminate the results of the single reports in the physiological context of the model systems used in these studies.

Utilizing CB1R and CB2R as pharmacological targets to modulate the autophagic activity is a promising treatment strategy for the treatment of different patho-physiological conditions and disease.”

http://www.ncbi.nlm.nih.gov/pubmed/25908257

Differential Pharmacological Regulation of Sensorimotor-Gating Deficit in CB1 Knockout Mice and Associated Neurochemical and Histological Alterations.

“The endocannabinoid system has been widely involved in the pathophysiology of sensorimotor gating deficits. The present study is aimed to evaluate the pharmacological modulation of the sensorimotor gating impairment induced by cannabinoid CB1 receptor (CB1r) deletion…

These data further support the important role of CB1r in sensorimotor gating regulation and the therapeutic usefulness of methylphenidate for the treatment of psychiatric disorders with associated pre-attentional deficits.”

http://www.ncbi.nlm.nih.gov/pubmed/25895455