Self-Medication of Somatic and Psychiatric Conditions Using Botanical Marijuana.

“As a complement to research evaluating botanical marijuana as a medical therapy for various somatic and psychiatric conditions, there is a growing body of research assessing marijuana users’ self-reports of the symptoms and conditions for which they use marijuana without a physician’s recommendation.

As part of two larger web-based surveys and one in-situ survey at an outdoor marijuana festival, we asked regular marijuana users if they consumed the drug without a physician’s recommendation and, if so, to describe (or select from a checklist) the conditions for which they used marijuana as a medication.

Participants reported using marijuana to self-medicate a wide variety of both somatic conditions (such as pain, diabetes, and irritable bowel syndrome) and psychiatric conditions (such as depression, anxiety, and insomnia).

Because fewer than half of the American states, and only a few countries, allow physicians to recommend medicinal marijuana, these findings may be of interest to clinicians as they treat patients, to lawmakers and policymakers as they consider legislation allowing physicians to recommend botanical marijuana for somatic and psychiatric conditions, and to researchers evaluating conditions that individuals elect to self-medicate using botanical marijuana.”

http://www.ncbi.nlm.nih.gov/pubmed/26595140

Involvement of opioid system in antidepressant-like effect of the cannabinoid CB1 receptor inverse agonist AM-251 after physical stress in mice.

“Cannabinoid inverse agonists possess antidepressant-like properties…

Numerous studies reported the interaction between opioid and cannabinoid pathways.

In this study, we used acute foot-shock stress in mice to investigate the involvement of opioid pathway in the antidepressant-like effect of the cannabinoid CB1 receptor inverse agonist AM-251.

In conclusion, the present study for the first time revealed the possible role of opioid signaling in the antidepressant-like properties of AM-251 in foot-shock stress model. “

http://www.ncbi.nlm.nih.gov/pubmed/26609670

Crosstalk between endocannabinoid and immune systems: a potential dysregulation in depression?

“The endocannabinoid (eCB) system, an endogenous lipid signaling system, appears to be dysregulated in depression. The role of endocannabinoids (eCBs) as potent immunomodulators, together with the accumulating support for a chronic low-grade inflammatory profile in depression, suggests a compelling hypothesis for a fundamental impairment in their intercommunication, in depression.

OBJECTIVE:

We aim to review previous literature on individual associations between the immune and eCB systems and depression. It will focus on peripheral and central mechanisms of crosstalk between the eCB and immune systems. A potential dysregulation in this crosstalk will be discussed in the context of depression.

RESULTS:

Investigations largely report a hypoactivity of the eCB system and increased inflammatory markers in individuals with depression. Findings depict a multifaceted communication whereby immunocompetent and eCB-related cells can both influence the suppression and enhancement of the other’s activity in both the periphery and central nervous system. A dysregulation of the eCB system, as seen in depression, appears to be associated with central and peripheral concentrations of inflammatory agents implicated in the pathophysiology of this illness.

CONCLUSION:

The eCB and immune systems have been individually associated with and implicated in pathogenic mechanisms of depression. Both systems tightly regulate the other’s activity. As such, a dysregulation in this crosstalk has potential to influence the onset and maintenance of this neuropsychiatric illness. However, few studies have investigated both systems and depression conjointly. This review highlights the demand to consider joint eCB-immune interactions in the pathoetiology of depression.”

http://www.ncbi.nlm.nih.gov/pubmed/26483037

Endocannabinoids and Mental Disorders.

“Preclinical and clinical data fully support the involvement of the endocannabinoid system in the etiopathogenesis of several mental diseases.

In this review we will briefly summarize the most common alterations in the endocannabinoid system, in terms of cannabinoid receptors and endocannabinoid levels, present in mood disorders (anxiety, posttraumatic stress disorder, depression, bipolar disorder, and suicidality) as well as psychosis (schizophrenia) and autism.

The arising picture for each pathology is not always straightforward; however, both animal and human studies seem to suggest that pharmacological modulation of this system might represent a novel approach for treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/26408164

Cannabinoid receptor activation prevents the effects of chronic mild stress on emotional learning and LTP in a rat model of depression.

“The endocannabinoid (eCB) system has recently emerged as a promising therapeutic target for the treatment of stress-related emotional disorders.

Recent data suggest that the eCB system could represent a new therapeutic target for the treatment of depression.

The findings suggest that enhancing cannabinoid signaling could represent a novel approach to the treatment of cognitive deficits that accompany stress-related depression.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3924526/

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

High Times for Painful Blues: The Endocannabinoid System in Pain-Depression Comorbidity.

“Depression and pain are two of the most debilitating disorders worldwide and have an estimated cooccurrence of up to 80%. Comorbidity of these disorders is more difficult to treat, associated with significant disability and impaired health-related quality of life than either condition alone, resulting in enormous social and economic cost.

Several neural substrates have been identified as potential mediators in the association between depression and pain, including neuroanatomical reorganization, monoamine and neurotrophin depletion, dysregulation of the hypothalamo-pituitary-adrenal axis, and neuroinflammation.

However, the past decade has seen mounting evidence supporting a role for the endogenous cannabinoid (endocannabinoid) system in affective and nociceptive processing, and thus, alterations in this system may play a key role in reciprocal interactions between depression and pain.

This review will provide an overview of the preclinical evidence supporting an interaction between depression and pain and the evidence supporting a role for the endocannabinoid system in this interaction.”

http://www.ncbi.nlm.nih.gov/pubmed/26342110

“The plant Cannabis sativa has been used as a medicine throughout the world for several thousand years, with reports of its use in treating painful symptoms appearing as early as 2600 BC. The principal psychoactive ingredient of Cannabis sativa, delta-9-tetrahydrocannabinol (Δ9-THC), was first identified in 1964, and subsequent studies to understand its mechanism of action led to the discovery of the endogenous cannabinoid (endocannabinoid) system… Because of the distribution of the endocannabinoid system throughout spinal and supraspinal regions, it is in a prime position to regulate neurophysiological activities such as affective and nociceptive processing… evidence suggests a prominent role for the endocannabinoid system in the interaction between depression and pain,” http://ijnp.oxfordjournals.org/content/early/2015/09/04/ijnp.pyv095.long

[The endocannabinoid system role in the pathogenesis of obesity and depression].

“Excessive consumption and obesity do not always have to be strictly pathological. The adjustment of food intake as well as the pleasure of eating are the results of the circulation of neurotransmitters, hormones and glucocorticoids which have an ability to regulate the activity of many receptors connected with G protein, including endocannabinoid receptors.

The key role of endocannabinoids in pathogenesis of obesity is their overproduction by adipose cells.

Endocannabinoids (eCBs) affect CB1 receptors and increase hunger, willingness to intake food, decrease peristalsis and delay stomach emptying.

In obese people increased levels of both central and peripheral endocannabinoids are observed. It may be connected with higher availability of endocannabinoid precursors to synthesis from adipose tissue and lipids.

Raised concentration of eCBs in the body may be the consequence of their catabolism dysfunction. There is a positive correlation between amount the number of receptors in the peripheral tissues and obesity increase.

It is thought that expression of CB1 receptors in mesolimbic system is connected with motivation to consume food in response to rewarding factor.

The appetite increase after cannabinoids use is probably caused by rewarding action of the consumed food and it results from excessive dopaminergic transmission in award system.

The pharmacological inhibition of endocannabinoids activity leads to weight loss, but may also have negative consequences such as decreased mood, reduced tolerance of pain, intensified anxiety, anhedonia, depressive symptoms, even suicidal thoughts.

In post mortem examinations a decrease in CB1 receptor density in grey matter of glial cells in patients with major depression was identified. The pleiotropic and extensive activity of endocannabinoid system can influence a range of neurotransmitters thereby modulating the psychiatric life phenomena, simultaneously being involved in metabolism control and energetic system of human body.

Hence it is a link between metabolic disorders and depression and anxiety disorders. Therefore, in obese people depressive comorbidity is higher and it significantly worsens prognosis and decreases life quality.”

http://www.ncbi.nlm.nih.gov/pubmed/26277182

Anxiety, Stress, and Fear Response in Mice with Reduced Endocannabinoid Levels.

Disruption of the endocannabinoid system through pharmacological or genetic invalidation of cannabinoid CB1 receptors has been linked to depression in humans and depression-like behaviors in mice.

We generated and used knockout mice lacking DAGL-α (Dagla-/-) to assess the behavioral consequences of reduced endocannabinoid levels in the brain…

Our findings demonstrate that the deletion of Dagla adversely affects the emotional state of animals and results in enhanced anxiety, stress, and fear responses.”

http://www.ncbi.nlm.nih.gov/pubmed/25981172

[Cannabinoids in medicine].

“Cannabinoids have been known for many centuries because of their various effects in healthcare. They are primarily effective in reducing nausea, vomiting, pain, anorexia, spasticity and depression. Some other effects are known, all seem to be mediated by cannabinoid receptors in the central nervous system. In the past years, medical use has been proven in several studies. Today, the therapeutical use of cannabinoids in medicine is increasing, and access was made easier. Especially in pain-management and palliative care, they seem to be a valuable therapeutic option.”

http://www.ncbi.nlm.nih.gov/pubmed/19165445

For whom the endocannabinoid tolls: Modulation of innate immune function and implications for psychiatric disorders.

“Over the past decade, there has been increasing evidence demonstrating that the endocannabinoid system can elicit potent modulatory effects on inflammatory processes, with clinical and preclinical evidence demonstrating beneficial effects on disease severity and symptoms in several inflammatory conditions.

This review examines the evidence supporting a modulatory effect of endocannabinoids on TLR-mediated immune responses both peripherally and centrally, and the implications for psychiatric disorders such as depression and schizophrenia.

CLASSES OF CANNABINOID-BASED PHARMACOLOGICAL AGENTS CITED IN THE REVIEW: Nonselective CB1/CB2 agonists: Δ9-THC, HU210, CP55940, WIN55,212-2 Selective CB2 agonists: JWH-015 FAAH inhibitors: URB597, AA-5HT MAGL/ABHD6 inhibitors: JZL184, MJN110, KML129, WWL70 Endocannabinoid reuptake inhibitors: UCM707, OMDM1/2, AM404.”

http://www.ncbi.nlm.nih.gov/pubmed/25794989