Beyond the CB1 Receptor: Is Cannabidiol the Answer for Disorders of Motivation?

“The Cannabis sativa plant has been used to treat various physiological and psychiatric conditions for millennia.

Current research is focused on isolating potentially therapeutic chemical constituents from the plant for use in the treatment of many central nervous system disorders.

Of particular interest is the primary nonpsychoactive constituent cannabidiol (CBD).

Unlike Δ9-tetrahydrocannabinol (THC), CBD does not act through the cannabinoid type 1 (CB1) receptor but has many other receptor targets that may play a role in psychiatric disorders.

Here we review preclinical and clinical data outlining the therapeutic efficacy of CBD for the treatment of motivational disorders such as drug addiction, anxiety, and depression.

Across studies, findings suggest promising treatment effects and potentially overlapping mechanisms of action for CBD in these disorders and indicate the need for further systematic investigation of the viability of CBD as a psychiatric pharmacotherapy.”

http://www.ncbi.nlm.nih.gov/pubmed/27023732

Prohedonic Effect of Cannabidiol in a Rat Model of Depression.

“Accumulating evidence suggests that cannabidiol (CBD) may be an effective and safe anxiolytic agent and potentially also an antidepressant.

 These findings extend the limited knowledge on the antidepressant effect of CBD, now shown for the first time in a genetic animal model of depression. These results suggest that CBD may be beneficial for the treatment of clinical depression and other states with prominent anhedonia.”

http://www.ncbi.nlm.nih.gov/pubmed/27010632

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

The effect of cannabinoids on the stretch reflex in multiple sclerosis spasticity.

“The aim of this observational study was to assess the efficacy of a tetrahydrocannabinol-cannabidiol (THC : CBD) oromucosal spray on spasticity using the stretch reflex in patients with multiple sclerosis (MS).

Numeric rating scale (NRS) for spasticity, modified Ashworth scale (MAS), and the stretch reflex were assessed before and during treatment in 57 MS patients with spasticity eligible for THC : CBD treatment.

A significant reduction in stretch reflex amplitude as well as significant reductions of NRS and MAS scores were observed. There was a low concordance between the three measures (stretch reflex, NRS, and MAS), likely related to the different aspects of muscle hypertonia assessed.

Stretch reflex responders were taking a significantly higher number of puffs, whereas no differences were found in the responders by the other scales, suggesting that a higher dosage would add benefit if tolerated.

The present study confirms the efficacy of cannabinoids in reducing spasticity in patients with MS, suggesting a higher sensitivity and specificity of the stretch reflex compared with other measures. As an objective and quantitative measure of spasticity, the stretch reflex is particularly useful to assess the effects of cannabinoids on spinal excitability and may play a role in future pharmacological studies.”

http://www.ncbi.nlm.nih.gov/pubmed/27003093

Effects of fixed or self-titrated dosages of Sativex on cannabis withdrawal and cravings.

“There is currently no pharmacological treatment approved for cannabis dependence. In this proof of concept study, we assessed the feasibility/effects of fixed and self-titrated dosages of Sativex (1:1, Δ9-tetrahydrocannabinol (THC)/cannabidiol (CBD)) on craving and withdrawal from cannabis among nine community-recruited cannabis-dependent subjects.

The results found in this proof of concept study warrant further systematic exploration of Sativex as a treatment option for cannabis withdrawal and dependence.”

http://www.ncbi.nlm.nih.gov/pubmed/26925704

Cannabinoids: Medical implications.

“Herbal cannabis has been used for thousands of years for medical purposes.

With elucidation of the chemical structures of tetrahydrocannabinol (THC) and cannabidiol (CBD) and with discovery of the human endocannabinoid system, the medical usefulness of cannabinoids has been more intensively explored.

While more randomized clinical trials are needed for some medical conditions, other medical disorders, like chronic cancer and neuropathic pain and certain symptoms of multiple sclerosis, have substantial evidence supporting cannabinoid efficacy.

While herbal cannabis has not met rigorous FDA standards for medical approval, specific well-characterized cannabinoids have met those standards.

Where medical cannabis is legal, patients typically see a physician who “certifies” that a benefit may result.

Physicians must consider important patient selection criteria such as failure of standard medical treatment for a debilitating medical disorder. Medical cannabis patients must be informed about potential adverse effects, such as acute impairment of memory, coordination and judgment, and possible chronic effects, such as cannabis use disorder, cognitive impairment, and chronic bronchitis.

Novel ways to manipulate the endocannbinoid system are being explored to maximize benefits of cannabinoid therapy and lessen possible harmful effects.

Key messages The medical disorders with the current best evidence that supports a benefit for cannabinoid use are the following: multiple sclerosis patient-reported symptoms of spasticity (nabiximols, nabilone, dronabinol, and oral cannabis extract), multiple sclerosis central pain or painful spasms (nabiximols, nabilone, dronabinol, and oral cannabis extract), multiple sclerosis bladder frequency (nabiximols), and chronic cancer pain/neuropathic pain (nabiximols and smoked THC).

Participating physicians should be knowledgeable about cannabinoids, closely look at the risk/benefit ratio, and consider certain important criteria in selecting a patient, such as: age, severity, and nature of the medical disorder, prior or current serious psychiatric or substance use disorder, failure of standard medical therapy as well as failure of an approved cannabinoid, serious underlying cardiac/pulmonary disease, agreement to follow-up visits, and acceptance of the detailed explanation of potential adverse risks.

The normal human endocannabinoid system is important in the understanding of such issues as normal physiology, cannabis use disorder, and the development of medications that may act as agonists or antagonists to CB1 and CB2.

By understanding the endocannabinoid system, it may be possible to enhance the beneficial effects of cannabinoid-related medication, while reducing the harmful effects.”

http://www.ncbi.nlm.nih.gov/pubmed/26912385

THC:CBD Observational Study Data: Evolution of Resistant MS Spasticity and Associated Symptoms.

“The prospective observational MObility ImproVEment (MOVE) 2 study is collecting real-life clinical outcomes data on patients with treatment-resistant multiple sclerosis (MS) spasticity treated with THC:CBD oromucosal spray in routine clinical practice. The MOVE 2 study has been ongoing in Italy, involving more than 30 MS centres across the country, since 2013.

RESULTS:

In the Italian cohort, THC:CBD oromucosal spray was added mainly to oral baclofen. Similar to MOVE 2-Germany, during 3 months’ observation, treatment discontinuations were limited and patients recorded meaningful improvements on the patient-based 0-10 numerical rating scale and physician-rated modified Ashworth scale at mean daily doses that were about one-third lower than those used in the RCT. Also, similar to MOVE 2-Germany, the proportion of patients reporting adverse events was about one-third of the rate recorded in the RCT.

CONCLUSIONS:

While MOVE 2-Italy continues, this interim analysis has enabled us to better define the place in therapy of THC:CBD oromucosal spray within the context of daily management of our patients with MS spasticity.”

http://www.ncbi.nlm.nih.gov/pubmed/26901343

THC:CBD in Daily Practice: Available Data from UK, Germany and Spain.

“A retrospective registry study and a prospective safety study of THC:CBD oromucosal spray are reported.

…no evidence of addiction, abuse or misuse.

The homogeneity between these observational studies supports the interest in THC:CBD oromucosal spray for management of MS spasticity in daily practice.”

http://www.ncbi.nlm.nih.gov/pubmed/26901342

http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/

Cannabinoid Receptor 2 Participates in Amyloid-β Processing in a Mouse Model of Alzheimer’s Disease but Plays a Minor Role in the Therapeutic Properties of a Cannabis-Based Medicine.

“The endogenous cannabinoid system represents a promising therapeutic target to modify neurodegenerative pathways linked to Alzheimer’s disease (AD).

The aim of the present study was to evaluate the specific contribution of CB2 receptor to the progression of AD-like pathology and its role in the positive effect of a cannabis-based medicine (1:1 combination of Δ9-tetrahidrocannabinol and cannabidiol) previously demonstrated to be beneficial in the AβPP/PS1 transgenic model of the disease.

A new mouse strain was generated by crossing AβPP/PS1 transgenic mice with CB2 knockout mice. Results show that lack of CB2 exacerbates cortical Aβ deposition and increases the levels of soluble Aβ40. However, CB2 receptor deficiency does not affect the viability of AβPP/PS1 mice, does not accelerate their memory impairment, does not modify tau hyperphosphorylation in dystrophic neurites associated to Aβ plaques, and does not attenuate the positive cognitive effect induced by the cannabis-based medicine in these animals.

These findings suggest a minor role for the CB2 receptor in the therapeutic effect of the cannabis-based medicine in AβPP/PS1 mice, but also constitute evidence of a link between CB2 receptor and Aβ processing.”

http://www.ncbi.nlm.nih.gov/pubmed/26890764

http://www.thctotalhealthcare.com/category/alzheimers-disease-ad/

The Endocannabinoid System in the Retina: From Physiology to Practical and Therapeutic Applications.

“Cannabis is one of the most prevalent drugs used in industrialized countries.

The main effects of Cannabis are mediated by two major exogenouscannabinoids: ∆9-tetrahydroxycannabinol and cannabidiol. They act on specific endocannabinoid receptors, especially types 1 and 2.

Mammals are endowed with a functional cannabinoid system including cannabinoid receptors, ligands, and enzymes.

This endocannabinoid signaling pathway is involved in both physiological and pathophysiological conditions with a main role in the biology of the central nervous system.

As the retina is a part of the central nervous system due to its embryonic origin, we aim at providing the relevance of studying the endocannabinoid system in the retina. Here, we review the distribution of the cannabinoid receptors, ligands, and enzymes in the retina and focus on the role of the cannabinoid system in retinal neurobiology.

This review describes the presence of the cannabinoid system in critical stages of retinal processing and its broad involvement in retinal neurotransmission, neuroplasticity, and neuroprotection.

Accordingly, we support the use of synthetic cannabinoids as new neuroprotective drugs to prevent and treat retinal diseases.

Finally, we argue for the relevance of functional retinal measures in cannabis users to evaluate the impact of cannabis use on human retinal processing.”

http://www.ncbi.nlm.nih.gov/pubmed/26881099

Cannabidiol Oil for Decreasing Addictive Use of Marijuana: A Case Report.

“This case study illustrates the use of cannabidiol (CBD) oil to decrease the addictive use of marijuana and provide anxiolytic and sleep benefits.

The second most abundant component-CBD-has been suggested to have the medicinal effects of decreasing anxiety, improving sleep, and other neuro-protective effects.

The mechanism of action for CBD has been suggested to be antagonistic to the psychoactive properties of THC in many locations within the central nervous system. Such action raises the issue of whether it might be beneficial to use CBD in isolation to facilitate withdrawal of marijuana use.

With use of the CBD oil, the patient reported being less anxious, as well as settling into a regular pattern of sleep. He also indicated that he had not used any marijuana since starting the CBD oil. With the decrease in the dosage to 18 mg, the patient was able to maintain his nonuse of marijuana.”

http://www.ncbi.nlm.nih.gov/pubmed/26807069