THC Total Health Care

A comprehensive research archive dedicated to the science of cannabis

Review of the neurological benefits of phytocannabinoids.

Posted on May 18, 2018 by David Worrell

“Numerous physical, psychological, and emotional benefits have been attributed to marijuana since its first reported use in 2,600 BC in a Chinese pharmacopoeia. The phytocannabinoids, cannabidiol (CBD), and delta-9-tetrahydrocannabinol (Δ9-THC) are the most studied extracts from cannabis sativa subspecies hemp and marijuana. CBD and Δ9-THC interact uniquely with the endocannabinoid system (ECS). Through direct and indirect actions, intrinsic endocannabinoids and plant-based phytocannabinoids modulate and influence a variety of physiological systems influenced by the ECS.

METHODS:

In 1980, Cunha et al. reported anticonvulsant benefits in 7/8 subjects with medically uncontrolled epilepsy using marijuana extracts in a phase I clinical trial. Since then neurological applications have been the major focus of renewed research using medical marijuana and phytocannabinoid extracts.

RESULTS:

Recent neurological uses include adjunctive treatment for malignant brain tumors, Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, neuropathic pain, and the childhood seizure disorders Lennox-Gastaut and Dravet syndromes. In addition, psychiatric and mood disorders, such as schizophrenia, anxiety, depression, addiction, postconcussion syndrome, and posttraumatic stress disorders are being studied using phytocannabinoids.

CONCLUSIONS:

In this review we will provide animal and human research data on the current clinical neurological uses for CBD individually and in combination with Δ9-THC. We will emphasize the neuroprotective, antiinflammatory, and immunomodulatory benefits of phytocannabinoids and their applications in various clinical syndromes.” https://www.ncbi.nlm.nih.gov/pubmed/29770251 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938896/]]>

Cannabinoid signalling in embryonic and adult neurogenesis: possible implications for psychiatric and neurological disorders.

Posted on May 17, 2018 by David Worrell

“Cannabinoid signalling modulates several aspects of brain function, including the generation and survival of neurons during embryonic and adult periods. The present review intended to summarise evidence supporting a role for the endocannabinoid system on the control of neurogenesis and neurogenesis-dependent functions. An understanding of the mechanisms by which cannabinoid signalling influences developmental and adult neurogenesis will help foster the development of new therapeutic strategies for neurodevelopmental, psychiatric and neurological disorders.” https://www.ncbi.nlm.nih.gov/pubmed/29764526 https://www.cambridge.org/core/journals/acta-neuropsychiatrica/article/cannabinoid-signalling-in-embryonic-and-adult-neurogenesis-possible-implications-for-psychiatric-and-neurological-disorders/E9DE9116DC604D976C9C7B0D2D254674

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Medical Cannabis for Pediatric Moderate to Severe Complex Motor Disorders.

Posted on May 17, 2018 by David Worrell

“A complex motor disorder is a combination of various types of abnormal movements that are associated with impaired quality of life (QOL). Current therapeutic options are limited. We studied the efficacy, safety, and tolerability of medical cannabis in children with complex motor disorder. This pilot study was approved by the institutional ethics committee. Two products of cannabidiol (CBD) enriched 5% oil formulation of cannabis were compared: one with 0.25% δ-9-tetrahydrocannabinol (THC) 20:1 group, the other with 0.83% THC 6:1 group. Patients aged 1 to 17 years (n = 25) with complex motor disorder were enrolled. The assigned medication was administered for 5 months. Significant improvement in spasticity and dystonia, sleep difficulties, pain severity, and QOL was observed in the total study cohort, regardless of treatment assignment. Adverse effects were rare and included worsening of seizures in 2 patients, behavioral changes in 2 and somnolence in 1.” https://www.ncbi.nlm.nih.gov/pubmed/29766748 http://journals.sagepub.com/doi/abs/10.1177/0883073818773028?journalCode=jcna

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Effects of CB2 and TRPV1 receptors’ stimulation in pediatric acute T-lymphoblastic leukemia

Posted on May 17, 2018 by David Worrell

“T-Acute Lymphoblastic Leukemia (T-ALL) is less frequent than B-ALL, but it has poorer outcome. For this reason new therapeutic approaches are needed to treat this malignancy.

The Endocannabinoid/Endovanilloid (EC/EV) system has been proposed as possible target to treat several malignancies, including lymphoblastic diseases. The EC/EV system is composed of two G-Protein Coupled Receptors (CB1 and CB2), the Transient Potential Vanilloid 1 (TRPV1) channel, their endogenous and exogenous ligands and enzymes. CB1 is expressed mainly in central nervous system while CB2 predominantly on immune and peripheral cells, therefore we chose to selectively stimulate CB2 and TRPV1.

We treated T-ALL lymphoblasts derived from 4 patients and Jurkat cells with a selective agonist at CB2 receptor: JWH-133 [100 nM] and an agonist at TRPV1 calcium channel: RTX [5 uM] at 6, 12 and 24 hours. We analyzed the effect on apoptosis and Cell Cycle Progression by a cytofluorimetric assays and evaluated the expression level of several target genes (Caspase 3, Bax, Bcl-2, AKT, ERK, PTEN, Notch-1, CDK2, p53) involved in cell survival and apoptosis, by Real-Time PCR and Western Blotting.

We observed a pro-apoptotic, anti-proliferative effect of these compounds in both primary lymphoblasts obtained from patients with T-ALL and in Jurkat cell line. Our results show that both CB2 stimulation and TRPV1 activation, can increase the apoptosis in vitro, interfere with cell cycle progression and reduce cell proliferation, indicating that a new therapeutic approach to T-cell ALL might be possible by modulating CB2 and TRPV1 receptors.”

http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=25052

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Δ9-Tetrahydrocannabinol induces endocannabinoid accumulation in mouse hepatocytes: antagonism by Fabp1 gene ablation.

Posted on May 17, 2018 by David Worrell

“Phytocannabinoids, such as Δ⁹–tetrahydrocannabinol (THC), bind and activate cannabinoid (CB) receptors, thereby “piggy-backing” on the same pathway’s endogenous endocannabinoids (ECs). The recent discovery that liver fatty acid binding protein-1 (FABP1) is the major cytosolic “chaperone” protein with high affinity for both Δ⁹-THC and ECs suggests that Δ⁹-THC may alter hepatic EC levels. Therefore, the impact of Δ⁹-THC or EC treatment on the levels of endogenous ECs, such as N-arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG), was examined in cultured primary mouse hepatocytes from WT and Fabp1 gene-ablated (LKO) mice. Δ⁹-THC alone or 2-AG alone significantly increased AEA and especially 2-AG levels in WT hepatocytes. LKO alone markedly increased AEA and 2-AG levels. However, LKO blocked/diminished the ability of Δ⁹-THC to further increase both AEA and 2-AG. In contrast, LKO potentiated the ability of exogenous 2-AG to increase the hepatocyte level of AEA and 2-AG. These and other data suggest that Δ⁹-THC increases hepatocyte EC levels, at least in part, by upregulating endogenous AEA and 2-AG levels. This may arise from Δ⁹-THC competing with AEA and 2-AG binding to FABP1, thereby decreasing targeting of bound AEA and 2-AG to the degradative enzymes, fatty acid amide hydrolase and monoacylglyceride lipase, to decrease hydrolysis within hepatocytes.” https://www.ncbi.nlm.nih.gov/pubmed/29414765 http://www.jlr.org/content/59/4/646

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Anandamide and endocannabinoid system: an attractive therapeutic approach for cardiovascular disease.

Posted on May 17, 2018 by David Worrell

“Cardiovascular disease is currently not adequately managed and has become one of the main causes of morbidity and mortality worldwide. Current therapies are inadequate in terms of preventing its progression. There are several limitations, such as poor oral bioavailability, side effects, low adherence to treatment, and high dosage frequency of formulations due to the short half-life of the active ingredients used, among others. This review aims to highlight the most relevant aspects of the relationship between the cardiovascular system and the endocannabinoid system, with special attention to the possible translational effect of the use of anandamide in cardiovascular health. The deep and detailed knowledge of this interaction, not always beneficial, and that for years has gone unnoticed, is essential for the development of new therapies. We discuss the most recent and representative results obtained in the field of basic research, referring to the aforementioned subject, emphasizing fundamentally the main role of nitric oxide, renal physiology and its deregulation in pathological processes.”

https://www.ncbi.nlm.nih.gov/pubmed/29764302

http://journals.sagepub.com/doi/10.1177/1753944718773690

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Effect of Cannabidiol on Drop Seizures in the Lennox-Gastaut Syndrome.

Posted on May 17, 2018 by David Worrell

“Cannabidiol has been used for treatment-resistant seizures in patients with severe early-onset epilepsy. We investigated the efficacy and safety of cannabidiol added to a regimen of conventional antiepileptic medication to treat drop seizures in patients with the Lennox-Gastaut syndrome, a severe developmental epileptic encephalopathy. Among children and adults with the Lennox-Gastaut syndrome, the addition of cannabidiol at a dose of 10 mg or 20 mg per kilogram per day to a conventional antiepileptic regimen resulted in greater reductions in the frequency of drop seizures than placebo.” https://www.ncbi.nlm.nih.gov/pubmed/29768152 https://www.nejm.org/doi/10.1056/NEJMoa1714631]]>

Medication overuse headache following repeated morphine, but not [INCREMENT]9-tetrahydrocannabinol administration in the female rat.

Posted on May 17, 2018 by David Worrell

“The potential of [INCREMENT]-tetrahydrocannabinol (THC) as a treatment for migraine depends on antinociceptive efficacy with repeated administration. Although morphine has good antinociceptive efficacy, repeated administration causes medication overuse headache (MOH) – a condition in which the intensity/frequency of migraine increases. The present study compared the effect of repeated morphine or THC administration on the magnitude and duration of migraine-like pain induced by a microinjection of allyl isothiocyanate (AITC) onto the dura mater of female rats. Acute administration of THC or morphine prevented AITC-induced depression of wheel running. This antinociception was maintained in rats treated repeatedly with THC, but not following repeated administration of morphine. Moreover, repeated morphine, but not THC administration, extended the duration of AITC-induced depression of wheel running. These data indicate that tolerance and MOH develop rapidly to morphine administration. The lack of tolerance and MOH to THC indicates that THC may be an especially effective long-term treatment against migraine.”

https://www.ncbi.nlm.nih.gov/pubmed/29462111

https://insights.ovid.com/crossref?an=00008877-900000000-99334

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Overcoming the Bell-Shaped Dose-Response of Cannabidiol by Using Cannabis Extract Enriched in Cannabidiol

Posted on May 17, 2018 by David Worrell

“Cannabidiol (CBD), a major constituent of Cannabis, has been shown to be a powerful anti-inflammatory and anti-anxiety drug, without exerting a psychotropic effect. However, when given either intraperitoneally or orally as a purified product, a bell-shaped dose-response was observed, which limits its clinical use.

In the present study, we have studied in mice the anti-inflammatory and anti-nociceptive activities of standardized plant extracts derived from the Cannabis sativa L., clone 202, which is highly enriched in CBD and hardly contains any psychoactive ingredients.

In stark contrast to purified CBD, the clone 202 extract, when given either intraperitoneally or orally, provided a clear correlation between the anti-inflammatory and anti-nociceptive responses and the dose, with increasing responses upon increasing doses, which makes this plant medicine ideal for clinical uses.

The clone 202 extract reduced zymosan-induced paw swelling and pain in mice, and prevented TNFα production in vivo. It is likely that other components in the extract synergize with CBD to achieve the desired anti-inflammatory action that may contribute to overcoming the bell-shaped dose-response of purified CBD.

We therefore propose that Cannabis clone 202 (Avidekel) extract is superior over CBD for the treatment of inflammatory conditions.” https://www.scirp.org/journal/PaperInformation.aspx?paperID=53912

“In conclusion, we recommend standardized plant extract of the Cannabis clone 202 for treatment of various inflammatory conditions.” https://file.scirp.org/Html/5-2500582_53912.htm

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A stimulus-responsive, in situ-forming, nanoparticle-laden hydrogel for ocular drug delivery

Posted on May 17, 2018 by David Worrell

“Most medications targeting optic neuropathies are administered as eye drops. However, their corneal penetration efficiencies are typically < 5%. There is a clear, unmet need for novel transcorneal drug delivery vehicles. To this end, we have developed a stimulus-responsive, in situ-forming, nanoparticle-laden hydrogel for controlled release of poorly bioavailable drugs into the aqueous humor of the eye. We subsequently tested the efficacy of our formulation in whole-eye experiments by loading the nanoparticles with cannabigerolic acid (CBGA). Our formulation exhibits over a 300% increase in transcorneal penetration over control formulations. We have successfully developed a stimulus-responsive, in situ-forming, nanoparticle-laden hydrogel for controlled release of poorly bioavailable drugs such as cannabinoids into the aqueous humor of the eye. Our therapeutic strategy leverages the proven potential of cannabinoids to confer neuroprotection to ganglion cells. This work paves the way for the introduction of novel products targeting ocular diseases to the market.” https://link.springer.com/article/10.1007/s13346-018-0504-x]]>