Monthly Archives: August 2019

The safety, tolerability, and effectiveness of PTL-101, an oral cannabidiol formulation, in pediatric intractable epilepsy: A phase II, open-label, single-center study.

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“Several works have reported on the antiepileptic impact of cannabis-based preparations in patients with treatment-resistant epilepsy (TRE). However, current formulations suffer from low bioavailability and side effects. PTL-101, an oral formulation containing highly purified cannabidiol (CBD) embedded in seamless gelatin matrix beadlets was designed to enhance bioavailability and maintain a constant gastrointestinal transit time.

RESULTS:

Sixteen patients (age: 9.1±3.4) enrolled in the study; 11 completed the full treatment program. The average maintenance dose was 13.6±4.2mg/kg. Patient adherence to treatment regimens was 96.3±9.9%. By the end of the treatment period, 81.9% and 73.4±24.6% (p<0.05) reductions from baseline median seizure count and monthly seizure frequency, respectively, were recorded. Responders’ rate was 56%; two patients became fully seizure-free. By study end, 8 (73%) caregivers reported an improved/very much improved condition, and 9 (82%) reported reduced/very much reduced seizure severity. Most commonly reported treatment-related adverse effects were sleep disturbance/insomnia, (4 (25.0%) patients), followed by somnolence, increased seizure frequency, and restlessness (3 patients each (18.8%)). None were serious or severe, and all resolved.

CONCLUSIONS:

PTL-101 was safe and tolerable for use and demonstrated a potent seizure-reducing effect among pediatric patients with TRE.”

https://www.ncbi.nlm.nih.gov/pubmed/31394352

https://www.epilepsybehavior.com/article/S1525-5050(19)30305-1/fulltext

Application device for THC:CBD oromucosal spray in the management of resistant spasticity: pre-production testing.

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 Publication Cover“Patients with multiple sclerosis spasticity (MSS) and upper limb/hand impairment who are taking 9-delta-tetrahydrocannabinol:cannabidiol (THC:CBD) oromucosal spray (Sativex®) may have difficulty self-administering their medication, possibly limiting adherence and treatment effectiveness.

A Class I EU device is available to support administration of THC:CBD spray. Pre-production testing was undertaken in a patient sample.

Results: Fifteen patients participated. Mean treatment time with THC:CBD spray was 4 (range: 0.1-6.1) years. 87% of participants ‘always’, ‘often’ or ‘sometimes’ had hand impairment, and 53% reported difficulty administering THC:CBD spray. Participants reported better application using the device (73%), with less strength required (54%). Most participants (93%) considered the instruction leaflet to be clear and many (66%) expressed interest in using the device. Most HCPs (93%) did not foresee any difficulties in use of the device.

Conclusion: The proposed adherence device was useful to address self-application difficulties with THC:CBD spray in our sample. Providing the device to MSS patients with upper limb/hand spasticity impairment may restore autonomy and support adherence to THC:CBD spray.”

https://www.ncbi.nlm.nih.gov/pubmed/31393179

https://www.tandfonline.com/doi/abs/10.1080/17434440.2019.1653182?journalCode=ierd20

Attitudes and Beliefs About Medical Usefulness and Legalization of Marijuana among Cancer Patients in a Legalized and a Nonlegalized State.

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View details for Journal of Palliative Medicine cover image “There is a growing preference for the use of marijuana for medical purposes, despite limited evidence regarding its benefits and potential safety risks. Legalization status may play a role in the attitudes and preferences toward medical marijuana(MM).

Objectives: The attitudes and beliefs of cancer patients in a legalized (Arizona) versus nonlegalized state (Texas) regarding medical and recreational legalization and medical usefulness of marijuana were compared.

 

Results: The majority of individuals support legalization of marijuana for medical use (Arizona 92% [85-97%] vs. Texas 90% [82-95%]; p = 0.81) and belief in its medical usefulness (Arizona 97% [92-99%] vs. Texas 93% [86-97%]; p = 0.33) in both states. Overall, 181 (91%) patients supported legalization for medical purposes whereas 80 (40%) supported it for recreational purposes (p < 0.0001). Patients preferred marijuana over current standard treatments for anxiety (60% [51-68%]; p = 0.003). Patients found to favor legalizing MM were younger (p = 0.027), had worse fatigue (p = 0.015), appetite (p = 0.004), anxiety (p = 0.017), and were Cut Down, Annoyed, Guilty, and Eye Opener-Adapted to Include Drugs (CAGE-AID) positive for alcohol/drugs (p < 0.0001).

Conclusion: Cancer patients from both legalized and nonlegalized states supported legalization of marijuana for medical purposes and believed in its medical use. The support for legalization for medical use was significantly higher than for recreational use in both states.”

https://www.ncbi.nlm.nih.gov/pubmed/31386595

https://www.liebertpub.com/doi/10.1089/jpm.2019.0218

Is Cannabis of Potential Value as a Therapeutic for Inflammatory Bowel Disease?

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“Cannabis is commonly used by patients with inflammatory bowel disease (IBD) to ameliorate their symptoms.

Patients claim that cannabis reduces pain, increases appetite, and reduces the need for other medications.

In conclusion, considering the mechanism of action of phytocannabinoids and the accumulating evidence of their anti-inflammatory effects in experimental and in vitro studies, it is reasonable to assume that cannabis can be of benefit in the treatment of IBD.”

https://www.ncbi.nlm.nih.gov/pubmed/31388856

https://link.springer.com/article/10.1007%2Fs10620-019-05763-8

Cannabinoid receptor-1 antagonism: a new perspective on treating a murine schistosomal liver fibrosis model.

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 SciELO - Scientific Electronic Library Online“Formation of schistosomal granulomata surrounding the ova can result in schistosomiasis-associated liver fibrosis (SSLF). The current standard of treatment is praziquantel (PZQ), which cannot effectively reverse SSLF.

The role of the cannabinoid (CB) receptor family in liver fibrosis has recently been highlighted.

This study aimed to assess the therapeutic effect of CB1 receptor antagonism in reversing SSLF in a murine model of Schistosoma mansoni infection.

MAIN CONCLUSIONS:

Combining PZQ with CB1 receptor antagonists yielded the best results in reversing SSLF. To our knowledge, this is the first study to test this regimen in S. mansoni infection.”

https://www.ncbi.nlm.nih.gov/pubmed/31389521

http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762019000100338&tlng=en

Cannabinoid CB2 Receptor Modulation by the Transcription Factor NRF2 is Specific in Microglial Cells.

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 “Nuclear factor erythroid 2-related factor 2 (NRF2) is a pleiotropic transcription factor that has neuroprotective and anti-inflammatory effects, regulating more than 250 genes. As NRF2, cannabinoid receptor type 2 (CB2) is also implicated in the preservation of neurons against glia-driven inflammation. To this concern, little is known about the regulation pathways implicated in CB2 receptor expression. In this study, we analyze whether NRF2 could modulate the transcription of CB2 in neuronal and microglial cells. Bioinformatics analysis revealed an antioxidant response element in the promoter sequence of the CB2 receptor gene. Further analysis by chemical and genetic manipulations of this transcription factor demonstrated that NRF2 is not able to modulate the expression of CB2 in neurons. On the other hand, at the level of microglia, the expression of CB2 is NRF2-dependent. These results are related to the differential levels of expression of both genes regarding the brain cell type. Since modulation of CB2 receptor signaling may represent a promising therapeutic target with minimal psychotropic effects that can be used to modulate endocannabinoid-based therapeutic approaches and to reduce neurodegeneration, our findings will contribute to disclose the potential of CB2 as a novel target for treating different pathologies.”

https://www.ncbi.nlm.nih.gov/pubmed/31385133

https://link.springer.com/article/10.1007%2Fs10571-019-00719-y

Δ9-Tetrahydrocannabinol suppresses monocyte-mediated astrocyte production of MCP-1 and IL-6 in a TLR7-stimulated human co-culture.

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Journal of Pharmacology and Experimental Therapeutics“Cannabis is widely used in the United States with an estimated prevalence of 9.5%. Certain cannabinoids in Cannabis sativa, in particular, Δ9-tetrahydrocannabinol (THC), possess immune modulating and anti-inflammatory activity. Depending on the context, the anti-inflammatory activity of cannabinoids may be beneficial, such as in treating inflammatory diseases, or detrimental to normal immune defense against pathogens. The potential beneficial impact of cannabinoids on chronic neuroinflammation has gained recent attention. Monocyte migration to the brain has been implicated as a key event in chronic neuroinflammation and in the etiology of central nervous system diseases including viral infection (e.g., HIV-associated neurocognitive disorder). In the brain, monocytes can contribute to neuroinflammation through interactions with astrocytes, including inducing astrocyte secretion of cytokines and chemokines. In a human co-culture system, monocyte-derived IL-1β due to toll-like receptor 7 (TLR7)-activation, has been identified to promote astrocyte production of MCP-1 and IL-6. THC treatment of TLR7-stimulated co-culture suppressed monocyte secretion of IL-1β resulting in decreased astrocyte production of MCP-1 and IL-6. Furthermore, THC displayed direct inhibition of monocytes, as TLR7-stimulated monocyte monocultures treated with THC also showed suppressed IL-1β production. The cannabinoid receptor 2 (CB2) agonist, JWH-015, impaired monocyte IL-1β production similar to that of THC, suggesting THC is, in part, acting through CB2. THC also suppressed key elements of the IL-1β production pathway, including IL1B mRNA levels and caspase-1 activity. Collectively, this study demonstrates that the anti-inflammatory properties of THC suppress TLR7-induced monocyte secretion of IL-1β, through CB2, which results in decreased astrocyte secretion of MCP-1 and IL-6.

SIGNIFICANCE STATEMENT: As cannabis use is highly prevalent in the United States and has putative anti-inflammatory properties, it is important to investigate the effect of cannabinoids on immune cell function. Furthermore, cannabinoids have garnered particular interest due to their potential beneficial effects on attenuating viral-induced chronic neuroinflammation. This study utilized a primary human co-culture system to demonstrate that the major psychotropic cannabinoid in cannabis, Δ9-tetrahydrocannabinol (THC) and a cannabinoid receptor-2 (CB2) selective agonist, suppress specific monocyte-mediated astrocyte inflammatory responses. In the context of viral-induced chronic neuroinflammation, the findings presented here suggest that cannabinoids via CB2 ligation may have beneficial anti-inflammatory effects.”

https://www.ncbi.nlm.nih.gov/pubmed/31383729

http://jpet.aspetjournals.org/content/early/2019/08/05/jpet.119.260661

Cannabis and Epilepsy.

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 Publication Cover“In recent years, the use of cannabidiol in the treatment of refractory epilepsy has been increasingly investigated and has been gaining public support as a novel way to treat these disorders.

Marijuana has been used for medical purposes for thousands of years, and a lot of research has been conducted over the last several decades into the chemistry and pharmacology of marijuana and its many compounds, including cannabidiol.

There are historical and recent scientific developments that support the use of cannabidiol in rare severe epilepsy syndromes.”

https://www.ncbi.nlm.nih.gov/pubmed/31385740

https://www.tandfonline.com/doi/abs/10.1080/15504263.2019.1645372?journalCode=wjdd20

Cannabidiol Regulates the Expression of Keratinocyte Proteins Involved in the Inflammation Process through Transcriptional Regulation.

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cells-logo “Cannabidiol (CBD), a natural phytocannabinoid without psychoactive effect, is a well-known anti-inflammatory and antioxidant compound.

The possibility of its use in cytoprotection of cells from harmful factors, including ultraviolet (UV) radiation, is an area of ongoing investigation. Therefore, the aim of this study was to evaluate the effect of CBD on the regulatory mechanisms associated with the redox balance and inflammation in keratinocytes irradiated with UVA [30 J/cm2] and UVB [60 mJ/cm2].

Spectrophotometric results show that CBD significantly enhances the activity of antioxidant enzymes such as superoxide dismutase and thioredoxin reductase in UV irradiated keratinocytes. Furthermore, despite decreased glutathione peroxidase and reductase activities, CBD prevents lipid peroxidation, which was observed as a decreased level of 4-HNE and 15d-PGJ2 (measured using GC/MS and LC/MS). Moreover, Western blot analysis of protein levels shows that, under stress conditions, CBD influences interactions of transcription factors Nrf2- NFκB by inhibiting the NFκB pathway, increasing the expression of Nrf2 activators and stimulating the transcription activity of Nrf2.

In conclusion, the antioxidant activity of CBD through Nrf2 activation as well as its anti-inflammatory properties as an inhibitor of NFκB should be considered during design of new protective treatments for the skin.”

https://www.ncbi.nlm.nih.gov/pubmed/31382646

https://www.mdpi.com/2073-4409/8/8/827

THE EFFECTS OF MEDICAL MARIJUANA DISPENSARIES ON ADVERSE OPIOID OUTCOMES

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 Publication cover image“As more states enact laws liberalizing marijuana use and the U.S. opioid epidemic surges to unprecedented levels, understanding the relationship between marijuana and opioids is growing increasingly important.

Using a unique self‐constructed marijuana dispensary dataset, I estimate the impact of increased marijuana access on opioid‐related harms.

I exploit within‐ and across‐state variation in dispensary openings and find county‐level prescription opioid‐related fatalities decline by 11% following the opening a dispensary.

The estimated dispensary effects are qualitatively similar for opioid‐related admissions to treatment facilities. These results are strongest for males and suggest a substitutability between marijuana and opioids.”

https://onlinelibrary.wiley.com/doi/full/10.1111/ecin.12825

“I find that core-based statistical areas (CBSAs) with dispensary openings experience a 20 percentage point relative decrease in painkiller treatment admissions over the first two years of dispensary operations.”

https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3012381

“Access to medical marijuana reduces opioid prescriptions”  https://www.health.harvard.edu/blog/access-to-medical-marijuana-reduces-opioid-prescriptions-2018050914509