Efficacy of CBD-enriched medical cannabis for treatment of refractory epilepsy in children and adolescents – An observational, longitudinal study.

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“The objective of this observational study was to evaluate the efficacy of medical cannabis for the treatment of refractory epilepsy.

Fifty-seven patients (age 1-20 years) with epilepsy of various etiologies were treated with Cannabis oil extract (CBD/THC ratio of 20:1) for at least 3 months (Median follow up time-18 months). Forty-Six Patients were included in the efficacy analysis. Average CBD dose was11.4 mg/kg/d.

Twenty-six patients (56%) had ≤50% reduction in mean monthly seizure frequency. There was no statistically significant difference in response rate among various epilepsy etiologies, and cannabis strain used.

Younger age at treatment onset (<10 years) and higher CBD dose (>11 mg/kg/d) were associated with better response to treatment. Adverse reactions were reported in 46% of patients and were the main reason for treatment cessation.

Our results suggest that adding CBD-enriched cannabis extract to the treatment regimen of patients with refractory epilepsy may result in a significant reduction in seizure frequency according to parental reports.”

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Dronabinol oral solution in the management of anorexia and weight loss in AIDS and cancer.

“The true incidence of anorexia secondary to human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) and cancer is not well classified owing to the fact that there is a lack of standardized definitions and recent clinical data in these settings.

Dronabinol, or Δ-9-tetrahydrocannabinol, is a synthetic molecule that closely mimics the action of Cannabis sativa L., a naturally occurring compound activated in the central nervous system by cannabinoid receptors.

Dronabinol exerts its effects by directly acting on the vomiting and appetite control centers in the brain, which in turn increases appetite and prevents vomiting.

In the USA, dronabinol is currently available in two dosage formulations – oral capsule and oral solution. While the oral capsule was initially approved by the US Food and Drug Administration in 1985, the recent approval of the oral solution in 2016 presents an “easy-to-swallow” alternative for patients using or intending to use dronabinol.

Dronabinol is indicated in adult patients with HIV/AIDS for the treatment of anorexia and weight loss. However, there is no approved indication in the setting of cancer-related anorexia and weight loss. This review aims at presenting available data on the use of oral dronabinol in the management of anorexia and weight loss in HIV/AIDS and cancer, as well as characterizing and highlighting the pharmacotherapeutic considerations of the newest formulation of dronabinol.”

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A Naturalistic Examination of the Perceived Effects of Cannabis on Negative Affect

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“Cannabis is commonly used to alleviate symptoms of negative affect. However, a paucity of research has examined the acute effects of cannabis on negative affect in everyday life.

The current study provides a naturalistic account of perceived changes in symptoms of depression, anxiety, and stress as a function of dose and concentration of Δ9tetrahydrocannabinol (THC) and cannabidiol (CBD).

Cannabis is commonly used to alleviate depression, anxiety, and stress. Indeed, one of the most commonly reported motives for cannabis use is to cope with stress, with 72% of daily cannabis users reporting use of cannabis to relax or relieve tension.

Results from the present study indicate that medical cannabis users report a substantial and significant reduction in symptoms of negative affect shortly after using cannabis.”

https://www.ncbi.nlm.nih.gov/pubmed/29656267

https://www.sciencedirect.com/science/article/pii/S0165032718303100

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The use of cannabis in supportive care and treatment of brain tumor

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“Anticancer Effects of Cannabinoids may be able to Prolong Life.

Cannabinoids are multitarget substances. Currently available are dronabinol (synthetic delta-9-tetrahydrocannabinol, THC), synthetic cannabidiol (CBD) the respective substances isolated and purified from cannabis, a refined extract, nabiximols (THC:CBD = 1.08:1.00); and nabilone, which is also synthetic and has properties that are very similar to those of THC.

Cannabinoids have a role in the treatment of cancer as palliative interventions against nausea, vomiting, pain, anxiety, and sleep disturbances. THC and nabilone are also used for anorexia and weight loss, whereas CBD has no orexigenic effect. The psychotropic effects of THC and nabilone, although often undesirable, can improve mood when administered in low doses. CBD has no psychotropic effects; it is anxiolytic and antidepressive.

Of particular interest are glioma studies in animals where relatively high doses of CBD and THC demonstrated significant regression of tumor volumes (approximately 50% to 95% and even complete eradication in rare cases). Concomitant treatment with X-rays or temozolomide enhanced activity further. Similarly, a combination of THC with CBD showed synergistic effects. Although many questions, such as on optimized treatment schedules, are still unresolved, today’s scientific results suggest that cannabinoids could play an important role in palliative care of brain tumor patients.

THC, a partial CB1, CB2 agonist, has the stigma of psychotropic effects that are mediated by CB1 stimulation. However, CB1 stimulation is necessary for improving mood and appetite and many other effects. At present, it is hard to imagine a better approach than adjusting THC doses individually to balance wanted versus unwanted effects. Generally, higher doses are needed to achieve analgesic and antiemetic effects. Even much higher, supraphysiologic oral doses would be needed to combat tumors.

Combinations were synergistic under many circumstances such as in pain and antitumor studies. Cannabinoids differ in their antitumor activities and probably in their mechanisms and targets, which is a rationale for combinations. However, for many pharmacological effects (except against tumors) roughly 10-times higher daily doses are needed for CBD compared to THC.

In summary, the endocannabinoid system is likely playing a crucial role in palliative care. The future will show whether an optimized treatment strategy with cannabinoids can also prolong life of brain tumor patients by their virtue to combat cancer cells.”

https://academic.oup.com/nop/article/4/3/151/2918616

“Cannabinoid Drug Prolongs the Life of Brain Tumor Patients in Phase II Trials”  https://labiotech.eu/gw-pharmaceuticals-brain-tumor/

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Ajulemic acid: potential treatment for chronic inflammation.

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“Ajulemic acid (AJA, CT-3, IP-751, JBT-101, anabasum) is a first-in-class, synthetic, orally active, cannabinoid-derived drug that preferentially binds to the CB2 receptor and is nonpsychoactive.

In preclinical studies, and in Phase 1 and 2 clinical trials, AJA showed a favorable safety, tolerability, and pharmacokinetic profile. It also demonstrated significant efficacy in preclinical models of inflammation and fibrosis. It suppresses tissue scarring and stimulates endogenous eicosanoids that resolve chronic inflammation and fibrosis without causing immunosuppression.

AJA is currently being developed for use in 4 separate but related indications including systemic sclerosis (SSc), cystic fibrosis, dermatomyositis (DM), and systemic lupus erythematosus. Phase 2 clinical trials in the first 3 targets demonstrated that it is safe, is a potential treatment for these orphan diseases and appears to be a potent inflammation-resolving drug with a unique mechanism of action, distinct from the nonsteroidal anti-inflammatory drug (NSAID), and will be useful for treating a wide range of chronic inflammatory diseases.

It may be considered to be a disease-modifying drug unlike most NSAIDs that only provide symptomatic relief. AJA is currently being evaluated in 24-month open-label extension studies in SSc and in skin-predominant DM. A Phase 3 multicenter trial to demonstrate safety and efficacy in SSc has recently been initiated.”

“Ajulemic acid, a synthetic cannabinoid acid, induces an antiinflammatory profile of eicosanoids in human synovial cells.”  http://www.ncbi.nlm.nih.gov/pubmed/18840450

“Ajulemic acid (CT3): a potent analog of the acid metabolites of THC.”  https://www.ncbi.nlm.nih.gov/pubmed/10903396

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The Endocannabinoid System, Aggression, and the Violence of Synthetic Cannabinoid Use, Borderline Personality Disorder, Antisocial Personality Disorder, and Other Psychiatric Disorders

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“While most human research has concluded that the active ingredient of marijuana, Δ9-tetrahydrocannabinol, tends to dampen rather than provoke aggression in acute doses, recent evidence supports a relationship between the ingestion of synthetic cannabinoids and emergence of violent or aggressive behavior.

To summarize, this paper will draw upon basic and clinical research to explain how the endocannabinoid system may contribute to the genesis of aggressive behavior.”

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Cannabis for Chronic Pain: Challenges and Considerations.

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“The National Academies of Sciences, Engineering, and Medicine has found substantial evidence that cannabis (plant) is effective for the treatment of chronic pain in adults, and moderate evidence that oromucosal cannabinoids (extracts, especially nabiximols) improve short-term sleep disturbances in chronic pain. ”

https://www.ncbi.nlm.nih.gov/pubmed/29637590

https://onlinelibrary.wiley.com/doi/abs/10.1002/phar.2115

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Therapeutic cannabinoids in multiple sclerosis: immunomodulation revisited.

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Cannabinoids are compounds with pleiotropic properties that act on the cannabinoid receptors, CB1 and CB2, and are divided into endocannabinoids, the endogenous ligands of these receptors, synthetic cannabinoids and phytocannabinoids.

The latter are derived from the plant Cannabis sativa. The therapeutic and psychoactive properties of this plant have been observed and used for centuries.

Of the over 60 compounds that are unique to Cannabis sativa, the substances that have been attributed the greatest therapeutic potential are Δ9 – tetrahydrocannabinol (THC) and cannabidiol (CBD), both of which, used alone or combined with each other, have become approved drugs.”

https://www.ncbi.nlm.nih.gov/pubmed/29633480

https://onlinelibrary.wiley.com/doi/abs/10.1111/ene.13658

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Cannabis Essential Oil: A Preliminary Study for the Evaluation of the Brain Effects.

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“We examined the effects of essential oil from legal (THC <0.2% w/v) hemp variety on the nervous system in 5 healthy volunteers. GC/EIMS and GC/FID analysis of the EO showed that the main components were myrcene and β-caryophyllene.

The experiment consisted of measuring autonomic nervous system (ANS) parameters; evaluations of the mood state; and electroencephalography (EEG) recording before treatment, during treatment, and after hemp inhalation periods as compared with control conditions. The results revealed decreased diastolic blood pressure, increased heart rate, and significant increased skin temperature.

The subjects described themselves as more energetic, relaxed, and calm.

The analysis EEG showed a significant increase in the mean frequency of alpha (8-13 Hz) and significant decreased mean frequency and relative power of beta 2 (18,5-30 Hz) waves. Moreover, an increased power, relative power, and amplitude of theta (4-8 Hz) and alpha brain waves activities and an increment in the delta wave (0,5-4 Hz) power and relative power was recorded in the posterior region of the brain.

These results suggest that the brain wave activity and ANS are affected by the inhalation of the EO of Cannabis sativa suggesting a neuromodular activity in cases of stress, depression, and anxiety.”

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Biphasic Effects of THC in Memory and Cognition.

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“A generally undesired effect of cannabis smoking is a reversible disruption of short term memory induced by delta-9-tetrahydrocannabinol (THC), the primary psychoactive component of cannabis.

However, this paradigm has been recently challenged by a group of scientists who have shown that THC is also able to improve neurological function in old animals when chronically administered at low concentrations.

Moreover, recent studies demonstrated that THC paradoxically promotes hippocampal neurogenesis, prevents neurodegenerative process occurring in Alzheimer Disease, protects from inflammation-induced cognitive damage and restores memory and cognitive function in old mice.

With the aim to reconcile these seemingly contradictory facts, the present work will show that such paradox can be explained within the framework of hormesis, defined as biphasic dose responses. ”

https://www.ncbi.nlm.nih.gov/pubmed/29574698

https://onlinelibrary.wiley.com/doi/abs/10.1111/eci.12920

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