Association of Cannabis With Cognitive Functioning in Adolescents and Young Adults: A Systematic Review and Meta-analysis

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“Question  Is frequent or heavy cannabis use associated with cognitive dysfunction in adolescents and young adults?

Findings  This systematic review and meta-analysis of 69 cross-sectional studies of 2152 cannabis users and 6575 comparison participants showed a small but significant overall effect size for reduced cognitive functioning in adolescents and young adults who reported frequent cannabis use. However, studies requiring abstinence from cannabis for longer than 72 hours had a very small, nonsignificant effect size.

Meaning  Although continued cannabis use may be associated with small reductions in cognitive functioning, results suggest that cognitive deficits are substantially diminished with abstinence.

Conclusions and Relevance  Associations between cannabis use and cognitive functioning in cross-sectional studies of adolescents and young adults are small and may be of questionable clinical importance for most individuals. Furthermore, abstinence of longer than 72 hours diminishes cognitive deficits associated with cannabis use. Although other outcomes (eg, psychosis) were not examined in the included studies, results indicate that previous studies of cannabis in youth may have overstated the magnitude and persistence of cognitive deficits associated with use.”

https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2678214?redirect=true

“Cannabis harm to teenagers’ brains ‘overstated’, finds study”  https://www.independent.co.uk/news/health/cannabis-marijuana-legalisation-harm-brain-intelligence-development-mental-health-a8311126.html

“Weed doesn’t make stoners permanently slow – study”  http://www.newshub.co.nz/home/health/2018/04/weed-doesn-t-make-stoners-permanently-slow-study.html

“Marijuana’s effects on young brains diminish 72 hours after use, research says”  https://www.cnn.com/2018/04/18/health/marijuana-cognitive-effects-study/index.html

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Medical Marijuana Use in Older Adults.

Journal of the American Geriatrics Society banner“Symptom management in older adults, including pain and distressing non-pain symptoms, can be challenging. Medications can cause side effects that worsen quality of life or create other symptoms, and polypharmacy itself can be detrimental in older adults. 

Cannabinoids may offer a way of managing selected symptoms with fewer side effects.

Medical marijuana is an important area of study for older adults because of the side effects of other medications. It is also important for Baby Boomers, who are likely to have more experience with marijuana than older adults of previous generations. Therefore, geriatricians should understand medical marijuana’s clinical indications, adverse effects, and legal context.

This article reviews the evidence regarding indications for and risks of medical marijuana use in older adults.”

https://www.ncbi.nlm.nih.gov/pubmed/29668039

https://onlinelibrary.wiley.com/doi/abs/10.1111/jgs.15346

“Our study finds that the therapeutic use of cannabis is safe and efficacious in the elderly population.” https://www.ncbi.nlm.nih.gov/pubmed/29398248

“Medical cannabis significantly safer for elderly with chronic pain than Opioids”  https://www.sciencedaily.com/releases/2018/02/180213111508.htm

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INSIGHT ON THE IMPACT OF ENDOCANNABINOID SYSTEM IN CANCER: A REVIEW.

British Journal of Pharmacology banner

“In the last decades, the endocannabinoid system has attracted a great interest in medicine and cancer disease is probably one of its most promising therapeutic areas.

On the one hand, endocannabinoid system expression has been found altered in numerous types of tumours compared to healthy tissue, and this aberrant expression has been related to cancer prognosis and disease outcome, suggesting a role of this system in tumour growth and progression that depends on cancer type.

On the other hand, it has been reported that cannabinoids exert an anticancer activity by inhibiting the proliferation, migration and/or invasion of cancer cells; and also tumour angiogenesis.

The endocannabinoid system may be considered as a new therapeutic target, although further studies to fully establish the effect of cannabinoids on tumour progression remain necessary.”

https://www.ncbi.nlm.nih.gov/pubmed/29663308

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Cannabis and Anti-Cancer Drugs: Societal Usage and Expected Pharmacological Interactions – A Review.

Fundamental & Clinical Pharmacology banner

“Cannabis is a plant that has been used for centuries to relieve a wide range of symptoms. Since the 1960s, interest in medical research into this plant has grown steadily. Already very popular for recreational use, a growing number of consumers not accustomed to using cannabis for psychoactive purposes, have begun to use it as an alternative or complement to mainstream pharmaceutical medicines. The principal unsubstantiated or “social” uses of cannabis are based mainly on data that is at best controversial, but usually not scientifically proven. The aim of this review is to identify the scientific basis and reasons that lead patients with cancer to consume cannabis, and also to identify whether there is a risk of interaction between cannabis and anti-cancer medicines through drug transporters (P-glycoprotein and other ABC-superfamily members) Cytochromes P450 (3A, 1A, 2B, 2C 2D families…) and glucuronyl-transferases.”

https://www.ncbi.nlm.nih.gov/pubmed/29660159

https://onlinelibrary.wiley.com/doi/abs/10.1111/fcp.12373

“Cannabinoids as Anticancer Drugs.”  https://www.ncbi.nlm.nih.gov/pubmed/28826542

“Targeting the endocannabinoid system as a potential anticancer approach.”  https://www.ncbi.nlm.nih.gov/pubmed/29390896

“Anticancer mechanisms of cannabinoids”   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791144/

http://www.thctotalhealthcare.com/tag/anticancer/

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Endocannabinoid system in systemic lupus erythematosus: first evidence for a deranged 2-arachidonoylglycerol metabolism.

The International Journal of Biochemistry & Cell Biology

“The endocannabinoid (eCB) system plays a key role in many physiological and pathological conditions and its dysregulation has been described in several rheumatological and autoimmune diseases. Yet, its possible alteration in systemic lupus erythematosus (SLE) has never been investigated.

Here, we aimed filling this gap in plasma and peripheral blood mononuclear cells (PBMCs) of patients with SLE and age- and sex- matched healthy subjects (HS).

In conclusion, our results demonstrate, for the first time, an alteration of eCB system in SLE patients. They represents the first step toward the understanding of the role of eCB system in SLE that likely suggest DAGL and 2-AG as potential biomarkers of SLE in easily accessible blood samples.

Our data provides proof-of-concept to the development of cannabis-based medicine as immune-modulating agents.”

https://www.ncbi.nlm.nih.gov/pubmed/29655919

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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.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.

Pharmacology Research & Perspectives banner

“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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Cannabinoid Type 1 Receptors are Upregulated During Acute Activation of Brown Adipose Tissue.

Diabetes

“Activating brown adipose tissue (BAT) could provide a potential approach for the treatment of obesity and metabolic disease in humans.

Obesity is associated with up-regulation of the endocannabinoid system, and blocking the cannabinoid type 1 receptor (CB1R) has been shown to cause weight loss and decrease cardiometabolic risk factors. These effects may partly be mediated via increased BAT metabolism, since there is evidence that CB1R antagonism activates BAT in rodents.

To investigate the significance of CB1R in BAT function, we quantified the density of CB1R in human and rodent BAT using the positron emission tomography (PET) radioligand [18F]FMPEP-d2 , and in parallel measured BAT activation with the glucose analogue [18F]FDG. Activation by cold exposure markedly increased CB1R density and glucose uptake in BAT of lean men. Similarly, β3-receptor agonism increased CB1R density in BAT of rats.

In contrast, overweight men with reduced BAT activity exhibited decreased CB1R in BAT, reflecting impaired endocannabinoid regulation. Image-guided biopsies confirmed CB1R mRNA expression in human BAT. Furthermore, CB1R blockade increased glucose uptake and lipolysis of brown adipocytes.

Our results highlight that CB1Rs are significant for human BAT activity, and the CB1R provide a novel therapeutic target for BAT activation in humans.”

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Reefer to the Rescue: The Dope on Cannabidiol as a Multi-Symptom Panacea for Dravet Syndrome

American Epilepsy Society

“Dravet syndrome (DS) is a debilitating developmental disorder typified by severe seizures and delayed onset of psychomotor deficits.

In addition to increasing the risk for sudden unexpected death in epilepsy (SUDEP), the medically refractory status epilepticus in DS can be life-threatening, which makes it crucial to identify drugs to reduce seizures.

The quest for a viable drug to limit seizures in DS has intersected with the recent excitement over the potential use of cannabinoids as antiepileptic agents, leading to extensive anecdotal reports of the potential for cannabinoids to limit seizures in DS

Cannabinoids are active derivatives of the marijuana plant, Cannabis sativa.

The study reveals a strong preclinical basis for the use of CBD in DS. They find that CBD pre-treatment reduces both duration and severity of thermally-induced behavioral seizures.

In conclusion, Kaplan and colleagues provide the first preclinical demonstration that CBD may help alleviate seizures in a mouse model of DS validating the translational potential of CBD in patients with DS.

The demonstration that CBD improves deficits in social interactions in DS launches an exciting therapeutic possibility of alleviating behavioral impairments that persist beyond the seizures and pave the way for mechanistic studies that could positively impact treatment of autism spectrum disorders.”

http://epilepsycurrents.org/doi/10.5698/1535-7597.18.2.118?code=amep-site

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