Author Archives: David Worrell

Cannabidiol partially blocks the sleepiness in hypocretin-deficient rats. Preliminary data.

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Image result for CNS Neurol Disord Drug Targets.“Excessive daytime sleepiness and cataplexy are among the symptoms of narcolepsy, a sleep disorder caused by the loss of hypocretin/orexin (HCRT/OX) neurons placed into the hypothalamus (LH). Several treatments for managing narcolepsy include diverse drugs to induce alertness, such as antidepressants, amphetamine, or modafinil, etc.

Recent evidence has shown that cannabidiol (CBD), a non-psychotropic derived from Cannabis sativa, shows positive therapeutic effects in neurodegenerative disorders, including Parkinson´s disease. Furthermore, CBD provokes alertness and enhances wake-related neurochemicals in laboratory animals. Thus, it is plausible to hypothesize that excessive somnolence observed in narcolepsy could be blocked by CBD.

Here, we determined whether systemic injection of CBD (5mg/Kg, i.p.) would block the sleepiness in a narcolepsy model.

Hourly analysis of sleep data showed that CBD blocked the sleepiness during the lights-off period across 7h post-injection in lesioned rats.

Taking together, these findings suggest that CBD might prevent sleepiness in narcolepsy.”

https://www.ncbi.nlm.nih.gov/pubmed/31642794

Acute and residual effects of smoked cannabis: Impact on driving speed and lateral control, heart rate, and self-reported drug effects

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 Drug and Alcohol Dependence“Although driving under the influence of cannabis is increasingly common among young adults, little is known about residual effects on driver behavior.

This study examined acute and residual effects of smoked cannabis on simulated driving performance of young cannabis users.

Methods

In this double-blind, placebo-controlled, parallel-group randomized clinical trial, cannabis users (1-4 days/week) aged 19-25 years were randomized with a 2:1 allocation ratio to receive active (12.5% THC) or placebo (0.009% THC) cannabis in a single 750 mg cigarette. A median split (based on whole-blood THC concentrations at the time of driving) was used to divide the active group into low and high THC groups. Our primary outcome was simulated driving performance, assessed 30 minutes and 24 and 48 hours after smoking. Secondary outcomes included blood THC concentrations, subjective drug effects, and heart rate.

Results

Ninety-six participants were randomized, and 91 were included in the final analysis (30 high THC, 31 low THC, 30 placebo). Mean speed (but not lateral control) significantly differed between groups 30 minutes after smoking cannabis (p ≤ 0.02); low and high THC groups decreased their speed compared to placebo. Heart rate, VAS drug effect and drug high increased significantly immediately after smoking cannabis and declined steadily after that. There was little evidence of residual effects in any of the measures.

Conclusion

Acutely, cannabis caused decreased speed, increased heart rate, and increases in VAS drug effect and drug high. There was no evidence of residual effects on these measures over the two days following cannabis administration.

Smoked cannabis (12.5% THC) led to an acute decrease in speed in young adults. There was no clear effect of smoked cannabis on lateral control. There was little evidence of residual effects of smoked cannabis on driving performance.”

https://www.sciencedirect.com/science/article/abs/pii/S0376871619304181

Cannabidiol and Cannabinoid Compounds as Potential Strategies for Treating Parkinson’s Disease and L-DOPA-Induced Dyskinesia.

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 “Parkinson’s disease (PD) and L-DOPA-induced dyskinesia (LID) are motor disorders with significant impact on the patient’s quality of life. Unfortunately, pharmacological treatments that improve these disorders without causing severe side effects are not yet available. Delay in initiating L-DOPA is no longer recommended as LID development is a function of disease duration rather than cumulative L-DOPA exposure.

Manipulation of the endocannabinoid system could be a promising therapy to control PD and LID symptoms.

In this way, phytocannabinoids and synthetic cannabinoids, such as cannabidiol (CBD), the principal non-psychotomimetic constituent of the Cannabis sativa plant, have received considerable attention in the last decade.

In this review, we present clinical and preclinical evidence suggesting CBD and other cannabinoids have therapeutic effects in PD and LID. Here, we discuss CBD pharmacology, as well as its neuroprotective effects and those of other cannabinoids.

Finally, we discuss the modulation of several pro- or anti-inflammatory factors as possible mechanisms responsible for the therapeutic/neuroprotective potential of Cannabis-derived/cannabinoid synthetic compounds in motor disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/31637586

https://link.springer.com/article/10.1007%2Fs12640-019-00109-8

Single-Dose Pharmacokinetics and Preliminary Safety Assessment with Use of CBD-Rich Hemp Nutraceutical in Healthy Dogs and Cats.

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animals-logo “The use of CBD-rich hemp products is becoming popular among pet owners with no long-term safety data related to consumption in adult dogs and cats.

The purpose of this study was to determine the single-dose oral pharmacokinetics of CBD, and to provide a preliminary assessment of safety and adverse effects during 12-week administration using a hemp-based product in healthy dogs and cats.

Serum chemistry and CBC results showed no clinically significant alterations, however one cat showed a persistent rise in alanine aminotransferase (ALT) above the reference range for the duration of the trial.

In healthy dogs and cats, an oral CBD-rich hemp supplement administered every 12 h was not detrimental based on CBC or biochemistry values.

Cats do appear to absorb or eliminate CBD differently than dogs, showing lower serum concentrations and adverse effects of excessive licking and head-shaking during oil administration.”

https://www.ncbi.nlm.nih.gov/pubmed/31635105

https://www.mdpi.com/2076-2615/9/10/832

Cannabinoid receptor type 1 modulates the effects of polyunsaturated fatty acids on memory of stressed rats.

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 Publication Cover“Memory and GABAergic activity in the hippocampus of stressed rats improve after n-3 polyunsaturated fatty acid (PUFA) supplementation.

On the other hand, cannabinoid receptor type 1 (CB1) strongly regulates inhibitory neurotransmission in the hippocampus. Speculation about a possible relation between stress, endocannabinoids, and PUFAs.

Here, we examined whether the effects of PUFAs on memory of chronically stressed rats depends on pharmacological manipulation of CB1 receptors.

Memory improved in the stressed rats that were treated with AM251 and/or n-3 PUFAs. Supplementation with n-6 PUFAs did not affect memory of stressed rats, but co-treatment with AM251 improved it, while co-treatment with WIN55,212-2 did not affect memory.

Our results demonstrate that activity of the CB1 receptors may modulate the effects of PUFAs on memory of stressed rats. This study suggests that endocannabinoids and PUFAs can both become a singular system by being self-regulated in limbic areas, so they control the effects of stress on the brain.”

https://www.ncbi.nlm.nih.gov/pubmed/31637966

https://www.tandfonline.com/doi/abs/10.1080/1028415X.2019.1659561?journalCode=ynns20

Utilization of medicinal cannabis for pain by individuals with spinal cord injury.

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Image result for spinal cord series and cases“A cross-sectional multi-center study using an on-line survey addressing utilization, knowledge, and perceptions of medicinal cannabis (MC) by people with spinal cord injury (SCI).

OBJECTIVE:

To characterize differences between current (CU), past (PU), and never users (NU) of MC with SCI; to determine why people with SCI use MC; to examine reports of MCs’ efficacy and tolerability by individuals with SCI.

SETTING:

Three academic medical centers in the United States.

METHODS:

Comparison of demographic and attitudinal differences between CU, PU, and NU and differences in the groups’ reports of pain, health, and quality of life (QOL). Evaluation of utilization patterns and perceived efficacy of MC among CU and PU and reports of side effects of MC versus prescription medications. Data were analyzed using either Chi Square, distribution-free exact statistics, or t-tests for continuous data.

RESULTS:

Among a nationwide sample (n = 353) of individuals with SCI, NU were less likely than CU and PU to believe that cannabis ought to be legalized and more likely to endorse risks of use. Current users and PU reported greater pain interference in daily life than did NU, but there were no between group differences in QOL or physical or emotional health. Current users and PU took MC to address pain (65.30%), spasms (63.30%), sleeplessness (32.70%), and anxiety (24.00%), and 63.30% reported it offered “great relief” from symptoms. Participants reported that MC is more effective and carries fewer side effects than prescription medications.

CONCLUSIONS:

Medicinal cannabis is an effective and well-tolerated treatment for a number of SCI-related symptoms.”

https://www.ncbi.nlm.nih.gov/pubmed/31632724

https://www.nature.com/articles/s41394-019-0208-6

Using cannabis for pain management after spinal cord injury: a qualitative study.

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Image result for spinal cord series and cases

“OBJECTIVES:

To explore why individuals with spinal cord injury (SCI) choose to use cannabis to manage their pain and their experiences in doing so.

RESULTS:

Eight individuals participated in this study. We interpreted six themes that captured the participants’ perspectives regarding their choice to, and perceptions of, using cannabis to manage SCI pain. Participants were motivated to use cannabis when other pain management strategies had been ineffective and were well-informed, knowledgeable cannabis consumers. Participants reported cannabis reduced their pain quickly and enabled them to engage in activities of daily living and participate in life roles without the drowsiness of traditional prescribed pain medication. Despite the positive aspects, participants were concerned about the irregularity of supply and inconsistent dosage.

CONCLUSIONS:

Findings show that cannabis is used to reduce pain after SCI and enable increased community participation. Findings suggest that future studies examining the efficacy of cannabinoids in managing pain include function and participation outcome measures rather than solely focusing on measuring pain intensity. Focusing on meaningful outcomes may contribute to a greater understanding of the experiences of people with SCI.”

https://www.ncbi.nlm.nih.gov/pubmed/31632740

https://www.nature.com/articles/s41394-019-0227-3

“Cannabis helps those with spinal cord injuries escape pain”  https://medicalxpress.com/news/2019-10-cannabis-spinal-cord-injuries-pain.html

Cannabidiol As A Novel Therapeutic Strategy For Oral Inflammatory Diseases: A Review Of Current Knowledge And Future Perspectives.

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Image result for altern ther health med “The high frequency and painful profile of inflammatory oral lesions and the lack of an effective drug protocol for their management stimulate the search for pharmacological alternatives for the treatment of these conditions. Cannabidiol is the major non-psychotropic constituent of Cannabis sativa, receiving lately scientific interest because of its potential in the treatment of inflammatory disorders such as asthma, colitis and arthritis. There is little published in the current literature about the use of cannabidiol in oral health. Among its many protective functions, the ability to attenuate inflammation through the modulation of cytokines and its antiedema and analgesic effects may be important features in the treatment of oral lesions. In this review, we suggest that cannabidiol can be useful in the management of oral inflammatory disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/31634872

Hemp seed polysaccharides protect intestinal epithelial cells from hydrogen peroxide-induced oxidative stress.

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International Journal of Biological Macromolecules“The purpose of this study was to investigate structure of Hemp seed polysaccharide (HSP) and the protective effect of HSP from H2O2-induced oxidative damage in IPEC-1 cells and the possible mechanism of this protection.

Analysis of monosaccharide composition and structure of two fractions HSP0 and HSP0.2 from polysaccharide of Hemp seed (HSPc) were analyzed by high performance liquid chromatography (HPLC) and Fourier transform infrared spectroscopy (FT-IR).

The results showed that both HSP0 and HSP0.2 contain sulfate groups, which are sulfated polysaccharides. In IPEC-1 cells model, the release of LDH and MDA was significantly decreased, and the activities of SOD, GSH-Px and CAT were significantly increased in HSP0 and HSP0.2-treated group. HSP0.2 dramatically increased the gene expression of antioxidant enzymes and phase II detoxification enzymes measured by real-time fluorescent quantitative reverse transcription-polymerase chain reaction (qRT-PCR). In addition, HSP0.2 up-regulated the expression level of intracellular transcription factor Nuclear factor erythroid-2-related factor 2 (Nrf2) and inhibited the level of Kelch-like ECH-associated protein 1 (Keap1) with Western blot analysis.

Collectively, the present study suggested that HSP0.2 has the protective effect of IPEC-1 cells against H2O2-induecd oxidative stress. This protection mechanism may be related to activation of the Keap1/Nrf2 signaling pathway.”

https://www.ncbi.nlm.nih.gov/pubmed/31108145

https://www.sciencedirect.com/science/article/pii/S0141813018372660?via%3Dihub

Hemp seed pill may improve chronic constipation of the elderly and reduce the burden of helpers.

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Logo of jfammpc“Chronic constipation is common but serious problem of the elderly.

Hemp seed pills had been used over 1000 years as a purgative in the traditional Chinese medicine, and moreover, had the data of double-blinded randomized control trial.

Japan Geriatric Society introduced hemp seed pill as one of choice for chronic constipation of elderly in their guideline.

Hemp seed pills might improve chronic constipation of elderly and reduce the burden of nursing stuffs.

Traditional Chinese medicine Hemp seed pill (麻子仁丸) could improve chronic constipation of elderly in the difficult case.”

https://www.ncbi.nlm.nih.gov/pubmed/31334198

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6618208/