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

Posted on April 27, 2015 by David

“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.

Posted on April 26, 2015 by David

“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.

Posted on April 25, 2015 by David

“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.

Posted on April 22, 2015 by David

“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

Tonic endocannabinoid-mediated modulation of GABA release is independent of the CB1 content of axon terminals.

Posted on April 22, 2015 by David

“The release of GABA from cholecystokinin-containing interneurons is modulated by type-1 cannabinoid receptors (CB1). Here we tested the hypothesis that the strength of CB1-mediated modulation of GABA release is related to the CB1 content of axon terminals.

Our data suggest that only a subpopulation of CB1s, within nanometre distances from their target Cav2.2 channels, are responsible for endocannabinoid-mediated modulation of GABA release.”

http://www.ncbi.nlm.nih.gov/pubmed/25891347

Cannabinoids Inhibit T-cells via Cannabinoid Receptor 2 in an in vitro Assay for Graft Rejection, the Mixed Lymphocyte Reaction

Posted on April 19, 2015 by David

“Cannabinoids are known to have anti-inflammatory and immunomodulatory properties.

Cannabinoid receptor 2 (CB2) is expressed mainly on leukocytes and is the receptor implicated in mediating many of the effects of cannabinoids on immune processes.

This study tested the capacity of Δ9-tetrahydrocannabinol (Δ9-THC) and of two CB2-selective agonists to inhibit the murine Mixed Lymphocyte Reaction (MLR), an in vitro correlate of graft rejection following skin and organ transplantation. Both CB2-selective agonists and Δ9-THC significantly suppressed the MLR in a dose dependent fashion…

Together, these data support the potential of this class of compounds as useful therapies to prolong graft survival in transplant patients.

Cannabinoids were reported to have effects on immune responses as early as the 1970s, but the basis for this activity was not understood until the cannabinoid receptors were cloned

Ideally, the anatomically disparate expression of CB1 and CB2 would allow for the use of compounds selective for CB2, and thus eliminate the unwanted psychoactive effects from CB1 activation, while maintaining the anti-inflammatory and immunosuppressive properties.

CB2-selective cannabinoids have been proposed as possible candidates to block graft rejection.

The results presented in this paper show that Δ9-THC, a mixed CB1/CB2 agonist, and two CB2-selective agonists can inhibit the Mixed Lymphocyte Reaction (MLR), an in vitro correlate of organ and skin graft rejection.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3864984/

Historical essay: An Arabic surgeon, Ibn al Quff’s (1232-1286) account on surgical pain relief.

Posted on April 19, 2015 by David

“This is a review of Ibn al Quff’s account of surgical pain relief in his surgical book Al Omdah, in which he mentioned the word anesthetic (Al moukhadder) and the involvement of physician (al tabbaaee) to give mixture of drugs to prevent pain in a surgical condition to relieve the patient from pain or to make surgical management possible.

Hich indicated one rare occasion to such description in Arabic medical texts. Methods of administration of these drugs were inhalation, ingestion and by rectal suppositories.

The drugs used in anesthetic sponges include all the drugs that are recorded in the modern literature of anesthesia. They are as follows: opium, mandrake, Hyocymus albus, belladonna, Cannabis sativus, Cannabisindica, wild lettuce.

The anesthetic sponge, mentioned in many references as an inhalation method, may be of symbolic value to surgery.”

http://www.ncbi.nlm.nih.gov/pubmed/25885079

“Ibn al-Quff (1233-1286 AD), a medieval Arab surgeon and physician. Abū’l-Faraj ibn Ya’qūb ibn Isāq Ibn al-Quff al-Karakī (1233-1286 AD), best known as Ibn al-Quff in the West, was a 13th century Arab physician-surgeon. During his lifetime, Ibn al-Quff made some important contributions to the art of healing. He authored several books and commentaries in the field of medicine, in particular surgery.” http://www.ncbi.nlm.nih.gov/pubmed/24585631

http://www.thctotalhealthcare.com/category/pain-2/

Cannabis in medicine: a national educational needs assessment among Canadian physicians.

Posted on April 19, 2015 by David

“There is increasing global awareness and interest in the use of cannabis for therapeutic purposes (CTP).

It is clear that health care professionals need to be involved in these decisions, but often lack the education needed to engage in informed discussions with patients. This study was conducted to determine the educational needs of Canadian physicians regarding CTP…

We have identified several key educational needs among Canadian physicians regarding CTP. These data can be used to develop resources and educational programs to support clinicians in this area, as well as to guide further research to inform these gaps.”

http://www.ncbi.nlm.nih.gov/pubmed/25888752

“History of cannabis as a medicine: a review”

http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-44462006000200015

http://www.thctotalhealthcare.com/

Cannabidiol, a non-psychoactive cannabinoid, leads to EGR2-dependent anergy in activated encephalitogenic T cells.

Posted on April 17, 2015 by David

“Cannabidiol (CBD), the main non-psychoactive cannabinoid, has been previously shown by us to ameliorate clinical symptoms and to decrease inflammation in myelin oligodendrocyte glycoprotein (MOG)35-55-induced mouse experimental autoimmune encephalomyelitis model of multiple sclerosis as well as to decrease MOG35-55-induced T cell proliferation and IL-17 secretion. However, the mechanisms of CBD anti-inflammatory activities are unclear.

We found that CBD leads to upregulation of CD69 and lymphocyte-activation gene 3 (LAG3) regulatory molecules on CD4+CD25-accessory T cells. This subtype of CD4+CD25-CD69+LAG3+ T cells has been recognized as induced regulatory phenotype promoting anergy in activated T cells.

Indeed, we observed that CBD treatment results in upregulation of EGR2 (a key T cell anergy inducer) mRNA transcription in stimulated TMOG cells. This was accompanied by elevated levels of anergy promoting genes such as IL-10 (anti-inflammatory cytokine), STAT5 (regulatory factor), and LAG3 mRNAs, as well as of several enhancers of cell cycle arrest (such as Nfatc1, Casp4, Cdkn1a, and Icos).

Moreover, CBD exposure leads to a decrease in STAT3 and to an increase in STAT5 phosphorylation in TMOG cells, positive and negative regulators of Th17 activity, respectively. In parallel, we observed decreased levels of major histocompatibility complex class II (MHCII), CD25, and CD69 on CD19+ B cells following CBD treatment, showing diminished antigen presenting capabilities of B cells and reduction in their pro-inflammatory functions.

CONCLUSIONS:

Our data suggests that CBD exerts its immunoregulatory effects via induction of CD4+CD25-CD69+LAG3+ cells in MOG35-55-activated APC/TMOG co-cultures. This is accompanied by EGR2-dependent anergy of stimulated TMOG cells as well as a switch in their intracellular STAT3/STAT5 activation balance leading to the previously observed decrease in Th17 activity.”

http://www.ncbi.nlm.nih.gov/pubmed/25880134

Full-text: http://www.jneuroinflammation.com/content/12/1/52

Regulation of inflammation by cannabinoids, the endocannabinoids 2-arachidonoyl-glycerol and arachidonoyl-ethanolamide, and their metabolites.

Posted on April 17, 2015 by David

“2-Arachidonoyl-glycerol (2-AG) and arachidonyl-ethanolamide (AEA) are endocannabinoids that have been implicated in many physiologic disorders, including obesity, metabolic syndromes, hepatic diseases, pain, neurologic disorders, and inflammation.

Their immunomodulatory effects are numerous and are not always mediated by cannabinoid receptors, reflecting the presence of an arachidonic acid (AA) molecule in their structure, the latter being the precursor of numerous bioactive lipids that are pro- or anti-inflammatory.

2-AG and AEA can thus serve as a source of AA but can also be metabolized by most eicosanoid biosynthetic enzymes, yielding additional lipids.

In this regard, enhancing endocannabinoid levels by using endocannabinoid hydrolysis inhibitors is likely to augment the levels of these lipids that could regulate inflammatory cell functions.

This review summarizes the metabolic pathways involved in the biosynthesis and metabolism of AEA and 2-AG, as well as the biologic effects of the 2-AG and AEA lipidomes in the regulation of inflammation.”

http://www.ncbi.nlm.nih.gov/pubmed/25877930