Author Archives: David Worrell

Cannabidiol exerts protective effects in an in vitro model of Parkinson’s disease activating AKT/mTOR pathway.

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Fitoterapia“Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the degeneration of the nigrostriatal dopaminergic pathway with loss of substantia nigra pars compacta neurons and dopamine depletion. Various natural compounds showed protective actions against PD.

In this work, the protective effects of cannabidiol (CBD), obtained from Cannabis sativa, were evaluated in retinoic acid differentiated SH-SY5Y cells exposed to 1-methyl-4-phenylpyridinium (MPP+), an in vitro PD model.

CBD counteracted the loss of cell viability caused by MPP+, reducing apoptosis as demonstrated by the reduction of Bax and caspase 3. Moreover, CBD reduced the nuclear levels of PARP-1. The protective effects of CBD seem to be mediated by the activation of ERK and AKT/mTOR pathways.

These data suggested the involvement of ERK in the modulation of autophagy. However, beclin 1 levels were not modified neither by MPP+ nor by CBD. These results indicated that CBD may exert preventive and protective actions in PD.”

https://www.ncbi.nlm.nih.gov/pubmed/32184097

https://www.sciencedirect.com/science/article/abs/pii/S0367326X20301350?via%3Dihub

Cannabinoids, Blood-Brain Barrier, and Brain Disposition.

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Image result for pharmaceutics“Potential therapeutic actions of the cannabinoids delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are based on their activity as analgesics, anti-emetics, anti-inflammatory agents, anti-seizure compounds.

THC and CBD lipophilicity and their neurological actions makes them candidates as new medicinal approaches to treat central nervous system (CNS) diseases. However, they show differences about penetrability and disposition in the brain.

The present article is an overview about THC and CBD crossing the blood-brain barrier (BBB) and their brain disposition. Several findings indicate that CBD can modify the deleterious effects on BBB caused by inflammatory cytokines and may play a pivotal role in ameliorating BBB dysfunction consequent to ischemia. Thus supporting the therapeutic potential of CBD for the treatment of ischemic and inflammatory diseases of CNS.

Cannabinoids positive effects on cognitive function could be also considered through the aspect of protection of BBB cerebrovascular structure and function, indicating that they may purchase substantial benefits through the protection of BBB integrity. Delivery of these cannabinoids in the brain following different routes of administration (subcutaneous, oral, and pulmonary) is illustrated and commented. Finally, the potential role of cannabinoids in drug-resistance in the clinical management of neurological or psychiatric diseases such as epilepsy and schizophrenia is discussed on the light of their crossing the BBB.”

https://www.ncbi.nlm.nih.gov/pubmed/32183416

 

Matched pilot study examining cannabis-based dronabinol for acute pain following traumatic injury.

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BMJ Journals“To determine whether adjunctive dronabinol, a licensed form of delta-9-tetrahydrocannabinol, reduces opioid consumption when used off-label for managing acute pain following traumatic injury.

CONCLUSIONS:

The results of this study suggest adjunctive dronabinol reduces opioid consumption following traumatic injury.

The opioid-sparing effect of dronabinol may be greater in patients who are marijuana users.”

https://www.ncbi.nlm.nih.gov/pubmed/32154376

https://tsaco.bmj.com/content/5/1/e000391

Marijuana use does not affect the outcomes of bariatric surgery.

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 SpringerLink“The decriminalization of marijuana and legalization of derived products requires investigation of their effect on healthcare-related outcomes. Unfortunately, little data are available on the impact of marijuana use on surgical outcomes.

We aimed to determine the effect of marijuana use on 30-day complications and 1-year weight loss following laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG).

RESULTS:

Excess BMI lost did not differ between marijuana users and controls at 3 weeks (23.0% vs 18.9%, p = 0.095), 3 months (42.0% vs 38.1%, p = 0.416), 6 months (60.6% vs 63.1%, p = 0.631), 1 year (78.2% vs 77.3%, p = 0.789), or 2 years (89.1% vs 74.5%, p = 0.604). No differences in the rate of major 30-day postoperative complications, including readmission, infection, thromboembolic events, bleeding events and reoperation rates, were found between groups. Follow-up rate at two years was lower in marijuana users (12.3% vs 27.4%, p = 0.023).

CONCLUSION:

This study suggests marijuana use has no impact on 30-day complications or weight loss following bariatric surgery, and should not be a contraindication to bariatric surgery.”

https://www.ncbi.nlm.nih.gov/pubmed/32166550

https://link.springer.com/article/10.1007%2Fs00464-020-07497-5

Cannabinoids Improve Gastrointestinal Symptoms in a Parenteral Nutrition-Dependent Patient With Chronic Intestinal Pseudo-Obstruction.

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Journal of Parenteral and Enteral Nutrition“Chronic intestinal pseudo-obstruction (CIPO) is a rare and challenging cause of pediatric intestinal failure, requiring long-term parenteral nutrition in most cases. Despite optimal management, some patients experience chronic abdominal pain and recurrent obstructive episodes with a major impact on their quality of life.

Cannabinoids have been successfully used in some conditions. However, their use in CIPO has never been reported in the literature.

We report a case of successful use of medicinal cannabinoids in a patient with CIPO, resulting in a significant reduction of abdominal pain, vomiting, and subocclusive episodes and increased appetite and weight, without major adverse events.

Although further observations are required to consolidate these findings, this case may be helpful for other patients suffering from the same condition.”

https://www.ncbi.nlm.nih.gov/pubmed/32181915

https://onlinelibrary.wiley.com/doi/abs/10.1002/jpen.1821

Analgesic Effects of Cannabinoids for Chronic Non-cancer Pain: a Systematic Review and Meta-Analysis with Meta-Regression.

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SpringerLink “There is growing interest in using cannabinoids for chronic pain.

We performed a systematic review and meta-analysis of randomized controlled trials to evaluate the analgesic efficacy and adverse effects of cannabinoids for chronic non-cancer pain.

PubMed, EMBASE, Web of Science, Cochrane CENTRAL and clinicaltrials.gov were searched up to December 2018. Information on the type, dosage, route of administration, pain conditions, pain scores, and adverse events were extracted for qualitative analysis. Meta-analysis of analgesic efficacy was performed. Meta-regression was performed to compare the analgesic efficacy for different pain conditions (neuropathic versus non-neuropathic pain). Risk of bias was assessed by The Cochrane Risk of Bias tool, and the strength of the evidence was assessed using the Grade of Recommendations Assessment, Development, and Evaluation (GRADE) approach.

Forty-three randomized controlled trials were included. Meta-analysis was performed for 33 studies that compared cannabinoids to placebo, and showed a mean pain score (scale 0-10) reduction of -0.70 (p < 0.001, random effect). Meta-regression showed that analgesic efficacy was similar for neuropathic and non-neuropathic pain (Difference = -0.14, p = 0.262).

Inhaled, oral, and oromucosal administration all provided statistically significant, but small reduction in mean pain score (-0.97, -0.85, -0.45, all p < 0.001). Incidence of serious adverse events was rare, and non-serious adverse events were usually mild to moderate. Heterogeneity was moderate.

The GRADE level of evidence was low to moderate. Pain intensity of chronic non-cancer patients was reduced by cannabinoids consumption, but effect sizes were small. Efficacy for neuropathic and non-neuropathic pain was similar.”

https://www.ncbi.nlm.nih.gov/pubmed/32172501

https://link.springer.com/article/10.1007%2Fs11481-020-09905-y

The role of the cannabinoid system in opioid analgesia and tolerance.

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“Opioid receptor agonist drugs, such as morphine, are very effective for treating chronic and severe pain; but, tolerance can develop with long-term use. Although there is a lot of information about the pathophysiological mechanisms of opioid tolerance, it is still not fully clarified. Suggested mechanisms for opioid tolerance include opioid receptor desensitisation, reduction of sensitivity G-proteins, activation of mitogen-activated protein kinase (MAPK), altered intracellular signaling pathway including nitric oxide, and activation of mammalian target of rapamycin (mTOR).

One way to reduce opioid tolerance and increase the analgesic potential is to use low doses. Combination of cannabinoids with opioids has been shown to manifest reduce the opioid dose. Experimental studies revealed an interaction of the endocannabinoid system and opioid antinociception.

Cannabinoid and opioid receptor systems use common pathways in the formation of analgesic effect and demonstrate their activity via G protein coupled receptors (GPCR). Cannabinoid drugs modulate opioid analgesic activity at a number of distinct levels within the cell, ranging from direct receptor associations, to post-receptor interactions through shared signal transduction pathways.

This review summarizes the data indicating that with combining cannabinoids and opioids drugs may be able to produce long-term analgesic effects, while preventing the opioid analgesic tolerance.”

https://www.ncbi.nlm.nih.gov/pubmed/32167427

http://www.eurekaselect.com/180186/article

Cannabinoid modulation of corticolimbic activation to threat in trauma-exposed adults: a preliminary study.

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 SpringerLink“Excessive fear and anxiety, coupled with corticolimbic dysfunction, are core features of stress- and trauma-related psychopathology, such as posttraumatic stress disorder (PTSD).

Interestingly, low doses of ∆9-tetrahydrocannabinol (THC) can produce anxiolytic effects, reduce threat-related amygdala activation, and enhance functional coupling between the amygdala and medial prefrontal cortex and adjacent rostral cingulate cortex (mPFC/rACC) during threat processing in healthy adults.

Together, these findings suggest the cannabinoid system as a potential pharmacological target in the treatment of excess fear and anxiety. However, the effects of THC on corticolimbic functioning in response to threat have not be investigated in adults with trauma-related psychopathology.

OBJECTIVE:

To address this gap, the present study tests the effects of an acute low dose of THC on corticolimbic responses to threat in three groups of adults: (1) non-trauma-exposed healthy controls (HC; n = 25), (2) trauma-exposed adults without PTSD (TEC; n = 27), and (3) trauma-exposed adults with PTSD (n = 19).

METHODS:

Using a randomized, double-blind, placebo-controlled, between-subjects design, 71 participants were randomly assigned to receive either THC or placebo (PBO) and subsequently completed a well-established threat processing paradigm during functional magnetic resonance imaging.

RESULTS:

In adults with PTSD, THC lowered threat-related amygdala reactivity, increased mPFC activation during threat, and increased mPFC-amygdala functional coupling.

CONCLUSIONS:

These preliminary data suggest that THC modulates threat-related processing in trauma-exposed individuals with PTSD, which may prove advantageous as a pharmacological approach to treating stress- and trauma-related psychopathology.”

https://www.ncbi.nlm.nih.gov/pubmed/32162103

https://link.springer.com/article/10.1007%2Fs00213-020-05499-8

Cannabis and the Cornea.

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Publication Cover

“While cannabis has the potential to reduce corneal pain, cannabinoids might induce side effects. This review article examines the effects of cannabinoids on the cornea. As more states and countries consider the legalization of adult cannabis use, health-care providers will need to identify ocular effects of cannabis consumption.

Methods: Studies included in this review examined the connection between cannabis and the cornea, more specifically anti-nociceptive and anti-inflammatory actions of cannabinoids. NCBI Databases from 1781 up to December 2019 were consulted.

Conclusion: More than half of the studies examined the therapeutic effects of cannabinoids on the cornea. As the field is still young, more studies should be conducted to develop safe cannabinoid treatments for corneal diseases.

 https://www.ncbi.nlm.nih.gov/pubmed/32159404
https://www.tandfonline.com/doi/abs/10.1080/09273948.2020.1726969?journalCode=ioii20

Influence of cannabinoids upon nerve-evoked skeletal muscle contraction.

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Neuroscience Letters“Endocannabinoids play important roles in regulating CNS synaptic function and peripheral metabolism, but cannabinoids can also act acutely to modulate contraction strength in skeletal muscle.

Nerve terminals and the skeletal muscle sarcolemma express components of the cannabinoid signaling system.

Endocannabinoids, N-arachidonylethanolamine (anandamide, AEA) and 2-arachidonoyl-glycerol (2-AG), are produced by skeletal muscle. They may be involved in the acute regulation of neuromuscular transmission, by adjusting the parameters for quantal acetylcholine release from the motor nerve terminal. Downstream of neuromuscular transmission, cannabinoids may also act to limit the efficiency of excitation-contraction coupling.

Improved understanding of the distinct signaling actions of particular cannabinoid compounds and their receptor/transduction systems will help advance our understanding of the role of endocannabinoids in skeletal muscle physiology.

Cannabinoids might also offer the potential to develop new pharmacotherapeutics to treat neuromuscular disorders that affect muscle strength.”

https://www.ncbi.nlm.nih.gov/pubmed/32156612

https://www.sciencedirect.com/science/article/abs/pii/S0304394020301701?via%3Dihub