Highly selective CB2 receptor agonist A836339 has gastroprotective effect on experimentally induced gastric ulcers in mice.

Naunyn-Schmiedeberg's Archives of Pharmacology

“Cannabinoid type 2 (CB2) receptors are distributed in central and peripheral tissues, including immunocytes and the gastrointestinal (GI) tract, suggesting that CB2 receptor agonists represent potential therapeutics in GI inflammatory states.

In this study, we investigated the effect of highly selective CB2 agonist, A836339, on the development of gastric lesions.

Activation of CB2 receptors exhibited gastroprotective effect through enhancement of anti-oxidative pathways in the stomach. Activation of CB2 receptors may thus become a novel therapeutic approach in the treatment of GU.”

Neuroprotective Effects of β-Caryophyllene against Dopaminergic Neuron Injury in a Murine Model of Parkinson’s Disease Induced by MPTP.

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“Parkinson’s disease (PD) is one of the most common neurodegenerative disorders and is characterized by the loss of dopaminergic neurons in the substantia nigra (SN). Although the causes of PD are not understood, evidence suggests that its pathogenesis is associated with oxidative stress and inflammation. Recent studies have suggested a protective role of the cannabinoid signalling system in PD. β-caryophyllene (BCP) is a natural bicyclic sesquiterpene that is an agonist of the cannabinoid type 2 receptor (CB2R). Previous studies have suggested that BCP exerts prophylactic and/or curative effects against inflammatory bowel disease through its antioxidative and/or anti-inflammatory action. The present study describes the neuroprotective effects of BCP in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced murine model of PD, and we report the results of our investigation of its neuroprotective mechanism in neurons and glial cells. In the murine model, BCP pretreatment ameliorated motor dysfunction, protected against dopaminergic neuronal losses in the SN and striatum, and alleviated MPTP-induced glia activation. Additionally, BCP inhibited the levels of inflammatory cytokines in the nigrostriatal system. The observed neuroprotection and inhibited glia activation were reversed upon treatment with the CB2R selective antagonist AM630, confirming the involvement of the CB2R. These results indicate that BCP acts via multiple neuroprotective mechanisms in our murine model and suggest that BCP may be viewed as a potential treatment and/or preventative agent for PD.”  https://www.ncbi.nlm.nih.gov/pubmed/28684694

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”  http://www.ncbi.nlm.nih.gov/pubmed/23138934

Cannabidiol Is a Potential Therapeutic for the Affective-Motivational Dimension of Incision Pain in Rats.

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“Drugs that interfere with the endocannabinoid system are alternatives for the management of clinical pain. Cannabidiol (CBD), a phytocannabinoid found in Cannabis sativa, has been utilized in preclinical and clinical studies for the treatment of pain. Herein, we evaluate the effects of CBD. The study provides evidence that CBD influences different dimensions of the response of rats to a surgical incision, and the results establish the rostral anterior cingulate cortex (rACC) as a brain area from which CBD evokes antinociceptive effects in a manner similar to the systemic administration of CBD. The present study has shown for the first time that CBD injected either systemically or into the rACC induces a long-lasting anti-allodynic effect with a bell-shaped dose-response curve in a rat model of incision pain.” https://www.ncbi.nlm.nih.gov/pubmed/28680401

Cannabinoids as therapeutic for PTSD

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“Limited efficacy for current pharmacotherapy for PTSD indicates that improved pharmacological treatments are needed. Neurobiological research points to cannabinoids as possible therapeutic agents of interest. Moreover, observational reports indicate that there is growing popular interest in therapeutic use of cannabinoids for the alleviation of trauma symptoms. The aim of this review was to present an up-to-date look at current research on the possible therapeutic value of cannabinoids for PTSD. Experimental, preclinical, and clinical findings are discussed.

Highlights

Neurobiological research indicates cannabis as possible pharmacological intervention for PTSD.

CBD and THC + CBD modulate fear memory in rodents.

Experimental data suggest CBD has acute anti-depressive and anxiolytic effects.

Data suggest THC reduces nightmares and OSA, while THC + CBD could reduce insomnia.

Randomized placebo-controlled human trials of cannabinoids for PTSD are underway.”

http://www.sciencedirect.com/science/article/pii/S2352250X16302342

https://www.researchgate.net/publication/311949481_Cannabinoids_as_therapeutic_for_PTSD

Cannabis as a Substitute for Opioid-Based Pain Medication: Patient Self-Report

“Prescription drug overdoses are the leading cause of accidental death in the United States. Alternatives to opioids for the treatment of pain are necessary to address this issue. Cannabis can be an effective treatment for pain, greatly reduces the chance of dependence, and eliminates the risk of fatal overdose compared to opioid-based medications. Medical cannabis patients report that cannabis is just as effective, if not more, than opioid-based medications for pain.

The results of this study provide implications from both a micro and macro level. First, from the macro level, there have been three previously published indicators of public health changes in states that permit medical cannabis: decreases in opioid related mortality, decreases in spending on opioids, and a decrease in traffic fatalities. While none of these studies shows a cause and effect relationship, they do suggest public health related population based changes in localities where cannabis can be accessed to treat pain. Given that the participants in this study reported a greater likelihood of using cannabis as a substitute in a less stigmatized and easily accessible environment, it makes sense why we would see these changes in locations where medical cannabis is sanctioned versus places where it is illegal.

At the micro level, there is a great deal of individual risk associated with prolonged use of opioids and perhaps even nonopioid-based pain medications. The prescribing of opioids has not been curbed in the United States, despite the growing number of fatal overdoses and reported dependence. Providing the patient with the option of cannabis as a method of pain treatment alongside the option of opioids might assist with pain relief in a safer environment with less risk. A society with less opioid dependent people will result in fewer public health harms.”

http://online.liebertpub.com/doi/10.1089/can.2017.0012

The case for cannabinoid CB1 receptors as a target for bronchodilator therapy for β-agonist resistant asthma.

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“Although b2-receceptor agonists are powerful bronchodilators and are at the forefront of asthma symptom relief, patients who use them frequently develop partial resistance to them. This can be a particularly serious problem during severe attacks, where high dose b2-agonist treatment is the front line therapy.

Alternative bronchodilators are urgently needed. In this article we review the evidence for the bronchodilator effects of the cannabinoid CB1 receptor tetrahydrocannabinol (THC) and suggest that the mechanism of action for these effects are sufficiently independent of the mechanisms of standard bronchodilators to warrant clinical investigation.

Specifically, clinical trials testing the bronchodilator effects of THC in b2 agonist resistant asthmatic patients would show whether THC could fill the role of rescue bronchodilator in cases of b2 agonist resistance.”  https://www.ncbi.nlm.nih.gov/pubmed/28641517

Guanfacine Attenuates Adverse Effects of Dronabinol (THC) on Working Memory in Adolescent-Onset Heavy Cannabis Users: A Pilot Study.

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“The cannabinoid-1 receptor (CB1R) agonist Δ9-tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, adversely effects working memory performance in humans. The α2A-adrenoceptor (AR) agonist guanfacine improves working memory performance in humans. The authors aimed to determine the effects of short-term (6 days) treatment with guanfacine on adverse cognitive effects produced by THC.

Employing a double-blind, placebo-controlled crossover design, the cognitive, subjective, and cardiovascular effects produced by oral THC (20 mg) administration were determined twice in the same cannabis users: once after treatment with placebo and once after treatment with guanfacine (3 mg/day).

Although THC increased visual analog scores of subjective effects and heart rate, these increases were similar during treatment with placebo and guanfacine. THC did not significantly affect performance of a recognition memory task or blood pressure while individuals were maintained on either treatment.

Although preliminary, these results suggest that guanfacine warrants further testing as a potential treatment for cannabis-induced cognitive deficits.” https://www.ncbi.nlm.nih.gov/pubmed/28641496   http://neuro.psychiatryonline.org/doi/10.1176/appi.neuropsych.16120328

“Guanfacine (brand name EstulicTenex and the extended release Intuniv; not to be confused with guaifenesin, an expectorant) is a sympatholytic drug used in the treatment of attention deficit hyperactivity disorder (ADHD), anxiety, and hypertension. It is a selective α2A receptor agonist https://en.wikipedia.org/wiki/Guanfacine

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Is cannabis treatment for anxiety, mood, and related disorders ready for prime time?

Depression and Anxiety

“Anxiety and related disorders are the most common mental conditions affecting the North American population. Despite their established efficacy, first-line antidepressant treatments are associated with significant side effects, leading many afflicted individuals to seek alternative treatments. Cannabis is commonly viewed as a natural alternative for a variety of medical and mental health conditions. Currently, anxiety ranks among the top five medical symptoms for which North Americans report using medical marijuana. However, upon careful review of the extant treatment literature, the anxiolytic effects of cannabis in clinical populations are surprisingly not well-documented. The effects of cannabis on anxiety and mood symptoms have been examined in healthy populations and in several small studies of synthetic cannabinoid agents but there are currently no studies which have examined the effects of the cannabis plant on anxiety and related disorders. In light of the rapidly shifting landscape regarding the legalization of cannabis for medical and recreational purposes, it is important to highlight the significant disconnect between the scientific literature, public opinion, and related policies. The aim of this article is to provide a comprehensive review of the current cannabis treatment literature, and to identify the potential for cannabis to be used as a therapeutic intervention for anxiety, mood, and related disorders. Searches of five electronic databases were conducted (PubMed, MEDLINE, Web of Science, PsychINFO, and Google Scholar), with the most recent in February 2017. The effects of cannabis on healthy populations and clinical psychiatric samples will be discussed, focusing primarily on anxiety and mood disorders.”  https://www.ncbi.nlm.nih.gov/pubmed/28636769   http://onlinelibrary.wiley.com/doi/10.1002/da.22664/abstract

“The endocannabinoid system and the treatment of mood and anxiety disorders. Collectively, both clinical and preclinical data argue that cannabinoid receptor signalling may be a realistic target in the development of a novel class of agent for the pharmacotherapy of mood and anxiety disorders.”  https://www.ncbi.nlm.nih.gov/pubmed/19839936

Assessing the role of serotonergic receptors in cannabidiol’s anticonvulsant efficacy.

“Cannabidiol (CBD) is a phytocannabinoid that has demonstrated anticonvulsant efficacy in several animal models of seizure. The current experiment validated CBD’s anticonvulsant effect using the acute pentylenetetrazol (PTZ) model.

While this work further confirms the anticonvulsant efficacy of CBD and supports its application in the treatment of human seizure disorders, additional research on CBD’s mechanism of action must be conducted.”

https://www.ncbi.nlm.nih.gov/pubmed/28624721

http://www.epilepsybehavior.com/article/S1525-5050(17)30122-1/fulltext

Quality of Life in Childhood Epilepsy in pediatric patients enrolled in a prospective, open-label clinical study with cannabidiol.

Epilepsia

“Recent clinical trials indicate that cannabidiol (CBD) may reduce seizure frequency in pediatric patients with certain forms of treatment-resistant epilepsy. Many of these patients experience significant impairments in quality of life (QOL) in physical, mental, and social dimensions of health. In this study, we measured the caregiver-reported Quality of Life in Childhood Epilepsy (QOLCE) in a subset of patients enrolled in a prospective, open-label clinical study of CBD. Results from caregivers of 48 patients indicated an 8.2 ± 9.9-point improvement in overall patient QOLCE (p < 0.001) following 12 weeks of CBD. Subscores with improvement included energy/fatigue, memory, control/helplessness, other cognitive functions, social interactions, behavior, and global QOL. These differences were not correlated to changes in seizure frequency or adverse events. The results suggest that CBD may have beneficial effects on patient QOL, distinct from its seizure-reducing effects; however, further studies in placebo-controlled, double-blind trials are necessary to confirm this finding.”

https://www.ncbi.nlm.nih.gov/pubmed/28617940

http://onlinelibrary.wiley.com/doi/10.1111/epi.13815/abstract