Early Phase in the Development of Cannabidiol as a Treatment for Addiction: Opioid Relapse Takes Initial Center Stage.

“Multiple cannabinoids derived from the marijuana plant have potential therapeutic benefits but most have not been well investigated, despite the widespread legalization of medical marijuana in the USA and other countries.

Therapeutic indications will depend on determinations as to which of the multiple cannabinoids, and other biologically active chemicals that are present in the marijuana plant, can be developed to treat specific symptoms and/or diseases.

Such insights are particularly critical for addiction disorders, where different phytocannabinoids appear to induce opposing actions that can confound the development of treatment interventions. Whereas Δ9-tetracannabinol has been well documented to be rewarding and to enhance sensitivity to other drugs, cannabidiol (CBD), in contrast, appears to have low reinforcing properties with limited abuse potential and to inhibit drug-seeking behavior.

Other considerations such as CBD’s anxiolytic properties and minimal adverse side effects also support its potential viability as a treatment option for a variety of symptoms associated with drug addiction.

However, significant research is still needed as CBD investigations published to date primarily relate to its effects on opioid drugs, and CBD’s efficacy at different phases of the abuse cycle for different classes of addictive substances remain largely understudied.

Our paper provides an overview of preclinical animal and human clinical investigations, and presents preliminary clinical data that collectively sets a strong foundation in support of the further exploration of CBD as a therapeutic intervention against opioid relapse.

As the legal landscape for medical marijuana unfolds, it is important to distinguish it from “medical CBD” and other specific cannabinoids, that can more appropriately be used to maximize the medicinal potential of the marijuana plant.”

http://www.ncbi.nlm.nih.gov/pubmed/26269227

The effects of dronabinol during detoxification and the initiation of treatment with extended release naltrexone.

“Evidence suggests that the cannabinoid system is involved in the maintenance of opioid dependence. We examined whether dronabinol, a cannabinoid receptor type 1 partial agonist, reduces opioid withdrawal and increases retention in treatment with extended release naltrexone (XR-naltrexone).

CONCLUSION:

Dronabinol reduced the severity of opiate withdrawal during acute detoxification but had no effect on rates of XR-naltrexone treatment induction and retention. Participants who elected to smoke marijuana during the trial were more likely to complete treatment regardless of treatment group assignment.”

http://www.ncbi.nlm.nih.gov/pubmed/26187456

Synthetic Cannabinoids.

“Synthetic cannabinoids (SCBs), also known under the brand names of “Spice,” “K2,” “herbal incense,” “Cloud 9,” “Mojo” and many others, are becoming a large public health concern due not only to their increasing use but also to their unpredictable toxicity and abuse potential. There are many types of SCBs, each having a unique binding affinity for cannabinoid receptors.

Although both Δ-tetrahydrocannabinol (THC) and SCBs stimulate the same receptors, cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2), studies have shown that SCBs are associated with higher rates of toxicity and hospital admissions than is natural cannabis.

This is likely due to SCBs being direct agonists of the cannabinoidreceptors, whereas THC is a partial agonist.

Furthermore, the different chemical structures of SCBs found in Spice or K2 may interact in unpredictable ways to elicit previously unknown, and the commercial products may have unknown contaminants.

The largest group of users is men in their 20s who participate in polydrug use.

The most common reported toxicities with SCB use based on studies using Texas Poison Control records are tachycardia, agitation and irritability, drowsiness, hallucinations, delusions, hypertension, nausea, confusion, dizziness, vertigo and chest pain. Acute kidney injury has also been strongly associated with SCB use.

Treatment mostly involves symptom management and supportive care.

More research is needed to identify which contaminants are typically found in synthetic marijuana and to understand the interactions between different SBCs to better predict adverse health outcomes.”

Roles for the endocannabinoid system in ethanol-motivated behavior.

“Alcohol use disorder represents a significant human health problem that leads to substantial loss of human life and financial cost to society. Currently available treatment options do not adequately address this human health problem, and thus, additional therapies are desperately needed.

The endocannabinoid system has been shown, using animal models, to modulate ethanol-motivated behavior, and it has also been demonstrated that chronic ethanol exposure can have potentially long-lasting effects on the endocannabinoid system.

For example, chronic exposure to ethanol, in either cell culture or preclinical rodent models, causes an increase in endocannabinoid levels that results in down-regulation of the cannabinoid receptor 1 (CB1) and uncoupling of this receptor from downstream G protein signaling pathways.

Using positron emission tomography (PET), similar down-regulation of CB1 has been noted in multiple regions of the brain in human alcoholic patients.

In rodents, treatment with the CB1 inverse agonist SR141716A (Rimonabant), or genetic deletion of CB1 leads to a reduction in voluntary ethanol drinking, ethanol-stimulated dopamine release in the nucleus accumbens, operant self-administration of ethanol, sensitization to the locomotor effects of ethanol, and reinstatement/relapse of ethanol-motivated behavior.

Although the clinical utility of Rimonabant or other antagonists/inverse agonists for CB1 is limited due to negative neuropsychiatric side effects, negative allosteric modulators of CB1 and inhibitors of endocannabinoid catabolism represent therapeutic targets worthy of additional examination.”

Psychological and social sequelae of cannabis and other illicit drug use by young people: a systematic review of longitudinal, general population studies.

“Use of illicit drugs, particularly cannabis, by young people is widespread and is associated with several types of psychological and social harm. These relations might not be causal. Causal relations would suggest that recreational drug use is a substantial public health problem…

All these associations seemed to be explicable in terms of non-causal mechanisms.

Available evidence does not strongly support an important causal relation between cannabis use by young people and psychosocial harm…

The lack of evidence of robust causal relations prevents the attribution of public health detriments to illicit drug use.”

http://www.ncbi.nlm.nih.gov/pubmed/15145631

Medical use of cannabis: an addiction medicine perspective.

“The use of cannabis for medical purposes, evident throughout history, has become a topic of increasing interest. Yet on the present medical evidence, cannabis-based treatments will only be appropriate for a small number of people in specific circumstances. Experience with cannabis as a recreational drug, and with use of psychoactive drugs that are prescribed and abused, should inform harm reduction in the context of medical cannabis.”  http://www.ncbi.nlm.nih.gov/pubmed/26059881

“A safer alternative: Cannabis substitution as harm reduction.”  http://www.ncbi.nlm.nih.gov/pubmed/25919477

Does cannabis affect dopaminergic signaling in the human brain? A systematic review of evidence to date.

“While abnormalities in multiple pathways may lead to schizophrenia, an abnormality in dopamine neurotransmission is considered to be the final common abnormality.

One would thus expect cannabis use to be associated with dopamine signaling alterations.

This is the first systematic review of all studies, both observational as well as experimental, examining the acute as well as chronic effect of cannabis or its main psychoactive ingredient, THC, on the dopamine system in man…

In man, there is as yet little direct evidence to suggest that cannabis use affects acute striatal dopamine release or affects chronic dopamine receptor status in healthy human volunteers. ”

http://www.ncbi.nlm.nih.gov/pubmed/26068702

Combined neuroprotective action of adenosine A1 and cannabinoid CB1 receptors against NMDA-induced excitotoxicity in the hippocampus.

“Both adenosine A1 and cannabinoid CB1 receptors trigger similar transduction pathways and protect against neurotoxic insults at the hippocampus, but their combined neuroprotective potential has not been investigated.

We set forth to assess the combined action of A1 and CB1 receptors against glutamate NMDA receptor-mediated excitotoxicity at the hippocampus…

The results suggest that both CB1 and A1 receptors produce additive cumulative neuroprotection against NMDA-induced excitotoxicity in the hippocampus.”

http://www.ncbi.nlm.nih.gov/pubmed/26065937

Cannabidiol as an Intervention for Addictive Behaviors: A Systematic Review of the Evidence.

“Drug addiction is a chronically relapsing disorder characterized by the compulsive desire to use drugs and a loss of control over consumption.

Cannabidiol (CBD), the second most abundant component of cannabis, is thought to modulate various neuronal circuits involved in drug addiction.

The goal of this systematic review is to summarize the available preclinical and clinical data on the impact of CBD on addictive behaviors.

MEDLINE and PubMed were searched for English and French language articles published before 2015. In all, 14 studies were found, 9 of which were conducted on animals and the remaining 5 on humans.

A limited number of preclinical studies suggest that CBD may have therapeutic properties on opioid, cocaine, and psychostimulant addiction, and some preliminary data suggest that it may be beneficial in cannabis and tobacco addiction in humans.

Further studies are clearly necessary to fully evaluate the potential of CBD as an intervention for addictive disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/26056464

“CBD is an exogenous cannabinoid that acts on several neurotransmission systems involved in addiction. Animal studies have shown the possible effects of CBD on opioid and psychostimulant addiction, while human studies presented some preliminary evidence of a beneficial impact of CBD on cannabis and tobacco dependence. CBD has several therapeutic properties on its own that could indirectly be useful in the treatment of addiction disorders, such as its protective effect on stress vulnerability and neurotoxicity… The dreadful burden of substance-use disorder worldwide, combined with the clear need for new medication in the addiction field, justifies the requirement of further studies to evaluate the potential of CBD as a new intervention for addictive behaviors.”  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4444130/

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

Is cannabis use associated with less opioid use among people who inject drugs?

“Clinical, experimental, and ethnographic research suggests that cannabis may be used to help manage pain.

Ethnographic research has revealed that some people are using cannabis to temper their illicit opioid use. We seek to learn if there is an association between cannabis use and the frequency of nonmedical opioid use among people who inject drugs (PWID).

…people who used cannabis used opioids less often than those who did not use cannabis…

There is a statistical association between recent cannabis use and lower frequency of nonmedical opioid use among PWID.

This may suggest that PWID use cannabis to reduce their pain and/or nonmedical use of opioids.”

http://www.ncbi.nlm.nih.gov/pubmed/26051162