Effects of short-term cannabidiol treatment on response to social stress in subjects at clinical high risk of developing psychosis.

 “Stress is a risk factor for psychosis and treatments which mitigate its harmful effects are needed.

Cannabidiol (CBD) has antipsychotic and anxiolytic effects.

OBJECTIVES:

We investigated whether CBD would normalise the neuroendocrine and anxiety responses to stress in clinical high risk for psychosis (CHR) patients.

RESULTS:

One-way analysis of variance (ANOVA) revealed a significant effect of group (HC, CHR-P, CHR-CBD (p = .005) on cortisol reactivity as well as a significant (p = .003) linear decrease. The change in cortisol associated with experimental stress exposure was greatest in HC controls and least in CHR-P patients, with CHR-CBD patients exhibiting an intermediate response. Planned contrasts revealed that the cortisol reactivity was significantly different in HC compared with CHR-P (p = .003), and in HC compared with CHR-CBD (p = .014), but was not different between CHR-P and CHR-CBD (p = .70). Across the participant groups (CHR-P, CHR-CBD and HC), changes in anxiety and experience of public speaking stress (all p’s < .02) were greatest in the CHR-P and least in the HC, with CHR-CBD participants demonstrating an intermediate level of change.

CONCLUSIONS:

Our findings show that it is worthwhile to design further well powered studies which investigate whether CBD may be used to affect cortisol response in clinical high risk for psychosis patients and any effect this may have on symptoms.”

https://www.ncbi.nlm.nih.gov/pubmed/31915861

“Antipsychotic effects of CBD have been linked to its effects on levels of the endogenous cannabinoid anandamide (AEA) potentially by inhibiting its catalytic enzyme fatty acid amide hydrolase (FAAH). Recent preclinical work has also suggested that CBD may block the anxiogenic effects of chronic stress that was associated with a concomitant decrease in the expression of FAAH following CBD treatment. To the best of our knowledge, this is the first study to have investigated the effects of short-term treatment with CBD on experimentally induced stress in the context of psychosis risk. Notwithstanding its limitations, the present study provides a strong rationale for future studies to investigate whether CBD may have potential to mitigate the harmful effects of stress in the course of daily life by attenuating the altered neuroendocrine and psychological responses to acute stress in CHR participants.”

https://link.springer.com/article/10.1007%2Fs00213-019-05442-6

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Targeting Cannabinoid Receptor Activation and BACE-1 Activity Counteracts TgAPP Mice Memory Impairment and Alzheimer’s Disease Lymphoblast Alterations.

“Alzheimer’s disease (AD), the leading cause of dementia in the elderly, is a neurodegenerative disorder marked by progressive impairment of cognitive ability. Patients with AD display neuropathological lesions including senile plaques, neurofibrillary tangles, and neuronal loss.

There are no disease-modifying drugs currently available. With the number of affected individuals increasing dramatically throughout the world, there is obvious urgent need for effective treatment strategy for AD.

The multifactorial nature of AD encouraged the development of multifunctional compounds, able to interact with several putative targets. Here, we have evaluated the effects of two in-house designed cannabinoid receptors (CB) agonists showing inhibitory actions on β-secretase-1 (BACE-1) (NP137) and BACE-1/butyrylcholinesterase (BuChE) (NP148), on cellular models of AD, including immortalized lymphocytes from late-onset AD patients.

We report here that NP137 and NP148 showed neuroprotective effects in amyloid-β-treated primary cortical neurons, and NP137 in particular rescued the cognitive deficit of TgAPP mice. The latter compound was able to blunt the abnormal cell response to serum addition or withdrawal of lymphoblasts derived from AD patients.

It is suggested that NP137 could be a good drug candidate for future treatment of AD.”

https://www.ncbi.nlm.nih.gov/pubmed/31898159

https://link.springer.com/article/10.1007%2Fs12035-019-01813-4

“The ideal treatment for AD should be able to modulate the disease through multiple mechanisms rather than targeting a single dysregulated pathway.” http://www.ncbi.nlm.nih.gov/pubmed/25147120

“These sets of data strongly suggest that THC could be a potential therapeutic treatment option for Alzheimer’s disease through multiple functions and pathways.” http://www.ncbi.nlm.nih.gov/pubmed/25024327

“In fact, exogenous and endogenous cannabinoids seem to be able to modulate multiple processes in AD” http://www.ncbi.nlm.nih.gov/pubmed/25147120

“Our results indicate that cannabinoid receptors are important in the pathology of AD and that cannabinoids succeed in preventing the neurodegenerative process occurring in the disease.” http://www.ncbi.nlm.nih.gov/pubmed/15728830

“Based on the complex pathology of AD, a preventative, multimodal drug approach targeting a combination of pathological AD symptoms appears ideal. Importantly, cannabinoids show anti-inflammatory, neuroprotective and antioxidant properties and have immunosuppressive effects.” http://www.ncbi.nlm.nih.gov/pubmed/22448595

“CBD treatment would be in line with preventative, multimodal drug strategies targeting a combination of pathological symptoms, which might be ideal for AD therapy.” http://www.ncbi.nlm.nih.gov/pubmed/27471947

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Cannabinoids and Opioids in the Treatment of Inflammatory Bowel Diseases.

Image result for clinical and translational gastroenterology“In traditional medicine, Cannabis sativa has been prescribed for a variety of diseases. Today, the plant is largely known for its recreational purpose, but it may find a way back to what it was originally known for: a herbal remedy. Most of the plant’s ingredients, such as Δ-tetrahydrocannabinol, cannabidiol, cannabigerol, and others, have demonstrated beneficial effects in preclinical models of intestinal inflammation. Endogenous cannabinoids (endocannabinoids) have shown a regulatory role in inflammation and mucosal permeability of the gastrointestinal tract where they likely interact with the gut microbiome. Anecdotal reports suggest that in humans, Cannabis exerts antinociceptive, anti-inflammatory, and antidiarrheal properties. Despite these reports, strong evidence on beneficial effects of Cannabis in human gastrointestinal diseases is lacking. Clinical trials with Cannabis in patients suffering from inflammatory bowel disease (IBD) have shown improvement in quality of life but failed to provide evidence for a reduction of inflammation markers. Within the endogenous opioid system, mu opioid receptors may be involved in anti-inflammation of the gut. Opioids are frequently used to treat abdominal pain in IBD; however, heavy opioid use in IBD is associated with opioid dependency and higher mortality. This review highlights latest advances in the potential treatment of IBD using Cannabis/cannabinoids or opioids.”

https://www.ncbi.nlm.nih.gov/pubmed/31899693

https://journals.lww.com/ctg/Abstract/latest/Cannabinoids_and_Opioids_in_the_Treatment_of.99898.aspx

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Effect of combined doses of Δ9-tetrahydrocannabinol and cannabidiol or tetrahydrocannabinolic acid and cannabidiolic acid on acute nausea in male Sprague-Dawley rats.

 “This study evaluated the potential of combined cannabis constituents to reduce nausea.

CONCLUSION:

Combinations of very low doses of CBD + THC or CBDA + THCA robustly reduce LiCl-induced conditioned gaping. Clinical trials are necessary to determine the efficacy of using single or combined cannabinoids as adjunct treatments with existing anti-emetic regimens to manage chemotherapy-induced nausea.”

https://www.ncbi.nlm.nih.gov/pubmed/31897571

https://link.springer.com/article/10.1007%2Fs00213-019-05428-4

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Cannabinoids as an Emerging Therapy for Posttraumatic Stress Disorder and Substance Use Disorders.

Related image “Posttraumatic Stress Disorder (PTSD) is a leading psychiatric disorder that mainly affects military and veteran populations but can occur in anyone affected by trauma. PTSD treatment remains difficult for physicians because most patients with PTSD do not respond to current pharmacological treatment. Psychotherapy is effective, but time consuming and expensive. Substance use disorder is often concurrent with PTSD, which leads to a significant challenge for PTSD treatment.

Cannabis has recently received widespread attention for the potential to help many patient populations. Cannabis has been reported as a coping tool for patients with PTSD and preliminary legalization data indicate Cannabis use may reduce the use of more harmful drugs, such as opioids. Rigorous clinical studies of Cannabis could establish whether Cannabis-based medicines can be integrated into treatment regimens for both PTSD and substance use disorder patients.”

https://www.ncbi.nlm.nih.gov/pubmed/31895187

https://insights.ovid.com/crossref?an=00004691-202001000-00005

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The Use of Cannabis as a Treatment for Epilepsy in Adult Patients: Are Side Effects a Limitation of Use?

 Related image“Marijuana is the dried leaves, stems, and flowers of a 1- to 5-m weed originating from Central Asia. The most common varieties are Cannabis sativa and Cannabis indica. It is usually inhaled as smoke but can also be used as a vapor, taken by mouth as a spray, ingested in tea or as butter in baked goods, or in capsule form and used as an oil. Cannabis has been widely used to treat many medical conditions such as multiple sclerosis symptoms, mood disorders, pain, sleep disorders, and seizures among others. Preclinical and clinical studies have been done over the past decade, among them there are few randomized placebo-controlled trials. In the last few years, Cannabis has been proposed as a potential therapy for patients with drug-resistant epilepsy. This review analyzes the best information about the use of cannabis in adult patients, reviewing aspects of efficacy and safety.”

https://www.ncbi.nlm.nih.gov/pubmed/31895185

https://insights.ovid.com/crossref?an=00004691-202001000-00003

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A North American History of Cannabis Use in the Treatment of Epilepsy.

 Related image“Cannabis has been used for millennia in religious ceremonies, for recreation and for its medicinal qualities. There are multiple accounts detailing the specific ailments cannabis has been used to treat, many of which have included epilepsy. Racial discrimination and political stigmatization led to prohibition, which limited both patients’ and researchers’ access to the drug through the 20th century. Recently, academic interest has been renewed in cannabis, especially regarding the modulation of cortical excitability via the human endocannabinoid system. Modern research has produced several promising studies regarding the treatment of epileptic encephalopathies. Legalization of marijuana in Canada has potentially allowed for further trials, but it is by no means an end to the controversy surrounding the treatment of epilepsy with cannabinoids.”

https://www.ncbi.nlm.nih.gov/pubmed/31895188

https://insights.ovid.com/crossref?an=00004691-202001000-00006

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The Endocannabinoid System and Synthetic Cannabinoids in Preclinical Models of Seizure and Epilepsy.

 Related image“Cannabinoids are compounds that are structurally and/or functionally related to the primary psychoactive constituent of Cannabis sativa, [INCREMENT]-tetrahydrocannabinol (THC). Cannabinoids can be divided into three broad categories: endogenous cannabinoids, plant-derived cannabinoids, and synthetic cannabinoids (SCs).

Recently, there has been an unprecedented surge of interest into the pharmacological and medicinal properties of cannabinoids for the treatment of epilepsies. This surge has been stimulated by an ongoing shift in societal opinions about cannabinoid-based medicines and evidence that cannabidiol, a nonintoxicating plant cannabinoid, has demonstrable anticonvulsant activity in children with treatment-refractory epilepsy.

The major receptors of the endogenous cannabinoid system (ECS)-the type 1 and 2 cannabinoid receptors (CB1R, CB2R)-have critical roles in the modulation of neurotransmitter release and inflammation, respectively; so, it is not surprising therefore that the ECS is being considered as a target for the treatment of epilepsy.

SCs were developed as potential new drug candidates and tool compounds for studying the ECS. Beyond the plant cannabinoids, an extensive research effort is underway to determine whether SCs that directly target CB1R, CB2R, or the enzymes that breakdown endogenous cannabinoids have anticonvulsant effects in preclinical rodent models of epilepsy and seizure.

This research demonstrates that many SCs do reduce seizure severity in rodent models and may have both positive and negative pharmacodynamic and pharmacokinetic interactions with clinically used antiepilepsy drugs. Here, we provide a comprehensive review of the preclinical evidence for and against SC modulation of seizure and discuss the important questions that need to be addressed in future studies.”

https://www.ncbi.nlm.nih.gov/pubmed/31895186

https://insights.ovid.com/crossref?an=00004691-202001000-00004

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Cannabis for Pediatric Epilepsy.

 Related image“Epilepsy is a chronic disease characterized by recurrent unprovoked seizures. Up to 30% of children with epilepsy will be refractory to standard anticonvulsant therapy, and those with epileptic encephalopathy can be particularly challenging to treat.

The endocannabinoid system can modulate the physiologic processes underlying epileptogenesis. The anticonvulsant properties of several cannabinoids, namely Δ-tetrahydrocannabinol and cannabidiol (CBD), have been demonstrated in both in vitro and in vivo studies.

Cannabis-based therapies have been used for millennia to treat a variety of diseases including epilepsy. Several studies have shown that CBD, both in isolation as a pharmaceutical-grade preparation or as part of a CBD-enriched cannabis herbal extract, is beneficial in decreasing seizure frequency in children with treatment-resistant epilepsy.

Overall, cannabis herbal extracts appear to provide greater efficacy in decreasing seizure frequency, but the studies assessing cannabis herbal extract are either retrospective or small-scale observational studies. The two large randomized controlled studies assessing the efficacy of pharmaceutical-grade CBD in children with Dravet and Lennox-Gastaut syndromes showed similar efficacy to other anticonvulsants. Lack of data regarding appropriate dosing and pediatric pharmacokinetics continues to make authorization of cannabis-based therapies to children with treatment-resistant epilepsy challenging.”

https://www.ncbi.nlm.nih.gov/pubmed/31895184

https://insights.ovid.com/crossref?an=00004691-202001000-00002

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β-Caryophyllene, a CB2-Receptor-Selective Phytocannabinoid, Suppresses Mechanical Allodynia in a Mouse Model of Antiretroviral-Induced Neuropathic Pain.

molecules-logo “Neuropathic pain associated with nucleoside reverse transcriptase inhibitors (NRTIs), therapeutic agents for human immunodeficiency virus (HIV), responds poorly to available drugs.

Smoked cannabis was reported to relieve HIV-associated neuropathic pain in clinical trials. Some constituents of cannabis (Cannabis sativa) activate cannabinoid type 1 (CB1) and cannabinoid type 2 (CB2) receptors. However, activation of the CB1 receptor is associated with side effects such as psychosis and physical dependence.

Therefore, we investigated the effect of β-caryophyllene (BCP), a CB2-selective phytocannabinoid, in a model of NRTI-induced neuropathic pain.

BCP prevents NRTI-induced mechanical allodynia, possibly via reducing the inflammatory response, and attenuates mechanical allodynia through CB2 receptor activation. Therefore, BCP could be useful for prevention and treatment of antiretroviral-induced neuropathic pain.”

https://www.ncbi.nlm.nih.gov/pubmed/31892132

https://www.mdpi.com/1420-3049/25/1/106

“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

“Beta-caryophyllene is a dietary cannabinoid.”   https://www.ncbi.nlm.nih.gov/pubmed/18574142

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