Special Considerations and Assessment in Patients with Multiple Sclerosis.

Physical Medicine and Rehabilitation Clinics of North America

“Multiple sclerosis is a progressive autoimmune neurologic disorder that may affect any region of the central nervous system. Spasticity in patients with multiple sclerosis can be debilitating and detrimental to the function and quality of life of patients. Treatment options include oral medications, chemodenervation, physical therapy, and modalities.

Cannabinoids in the form of a delta-9-tetrahydrocannabinol/cannabidiol oro-mucosal spray has been shown to be effective in addressing spasticity in multiple sclerosis.

Successful treatment of spasticity will be integrated, multimodal, and individualized.”

https://www.ncbi.nlm.nih.gov/pubmed/30626509

https://www.sciencedirect.com/science/article/pii/S1047965118307617?via%3Dihub

Cannabidiol in Anxiety and Sleep: A Large Case Series.

“Cannabidiol (CBD) is one of many cannabinoid compounds found in cannabis. It does not appear to alter consciousness or trigger a “high.”

A recent surge in scientific publications has found preclinical and clinical evidence documenting value for CBD in some neuropsychiatric disorders, including epilepsy, anxiety, and schizophrenia. Evidence points toward a calming effect for CBD in the central nervous system. Interest in CBD as a treatment of a wide range of disorders has exploded, yet few clinical studies of CBD exist in the psychiatric literature.

OBJECTIVE:

To determine whether CBD helps improve sleep and/or anxiety in a clinical population.

DESIGN:

A large retrospective case series at a psychiatric clinic involving clinical application of CBD for anxiety and sleep complaints as an adjunct to usual treatment. The retrospective chart review included monthly documentation of anxiety and sleep quality in 103 adult patients.

MAIN OUTCOME MEASURES:

Sleep and anxiety scores, using validated instruments, at baseline and after CBD treatment.

RESULTS:

The final sample consisted of 72 adults presenting with primary concerns of anxiety (n = 47) or poor sleep (n = 25). Anxiety scores decreased within the first month in 57 patients (79.2%) and remained decreased during the study duration. Sleep scores improved within the first month in 48 patients (66.7%) but fluctuated over time. In this chart review, CBD was well tolerated in all but 3 patients.

CONCLUSION:

Cannabidiol may hold benefit for anxiety-related disorders. Controlled clinical studies are needed.”

https://www.ncbi.nlm.nih.gov/pubmed/30624194

http://www.thepermanentejournal.org/issues/2019/winter/6960-cannabis.html

Medical Cannabis Users’ Comparisons between Medical Cannabis and Mainstream Medicine.

 Publication Cover“An evidence-based approach is needed to shape policies and practices regarding medical cannabis, thereby reducing harm and maximizing benefits to individuals and society.

This project assesses attitudes towards and utilization of medical cannabis and the mainstream healthcare system among medical cannabis users. The research team administered brief hard copy surveys to 450 adults attending an annual public event advocating for cannabis law reform.

Among usable responses (N = 392), the majority (78%) reported using cannabis to help treat a medical or health condition.

Medical cannabis users reported a greater degree of use of medical cannabis and a greater degree of trust in medical cannabis compared to mainstream healthcare.

In comparison to pharmaceutical drugs, medical cannabis users rated cannabis better on effectiveness, side effects, safety, addictiveness, availability, and cost.

Due to the medical use of cannabis, 42% stopped taking a pharmaceutical drug and 38% used less of a pharmaceutical drug.

A substantial proportion (30%) reported that their mainstream healthcare provider did not know that they used medical cannabis.

Other issues identified included lack of access to mainstream healthcare, self-initiated treatment of health issues, little knowledge of psychoactive content, and heavy cannabis use.”

https://www.ncbi.nlm.nih.gov/pubmed/30616501

https://www.tandfonline.com/doi/abs/10.1080/02791072.2018.1563314?journalCode=ujpd20

“A Growing Number of People Are Trading Their Pain Meds for Weed, Study Finds. As more states legalize marijuana, a new study shows that many patients are choosing medical cannabis to supplement or even replace pharmaceutical drugs. Nearly half of users in the study said they’d completely stopped taking a pharmaceutical drug because of medical marijuana.” https://www.menshealth.com/health/a25953041/medical-marijuana-pain-cannabis-prescription-drugs-study/

Epidiolex (Cannabidiol): A New Hope for Patients With Dravet or Lennox-Gastaut Syndromes.

 SAGE Journals

“OBJECTIVE: To review the efficacy, safety, pharmacology and pharmacokinetics of pure, plant-derived cannabidiol (CBD; Epidiolex) in the treatment of Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS).

DATA SYNTHESIS: Pure, plant-based CBD is a pharmaceutical grade extract that exhibits clinically significant antiseizure properties, with a hypothesized multimodal mechanism of action. In the GWPCARE trial series, CBD displayed superior efficacy in reducing key seizure frequencies (convulsive seizures in DS; drop seizures in LGS) by 17% to 23% compared with placebo as adjunctive therapy to standard antiepileptic drugs in patients 2 years of age and older. Common adverse effects were somnolence, diarrhea, and elevated hepatic transaminases. Noteworthy drug-drug interactions included clobazam, valproates, and significant inducers/inhibitors of CYP2C19 and 3A4 enzymes.

Relevance to Patient Care and Clinical Practice: A discussion regarding CBD dosing, administration, adverse effects, monitoring parameters, and interactions is provided to guide clinicians. CBD offers patients with DS and LGS a new treatment option for refractory seizures.

CONCLUSION:

This is the first cannabis-derived medication with approval from the US Food and Drug Administration. This CBD formulation significantly reduces seizures as an adjunct to standard antiepileptic therapies in patients ≥2 years old with DS and LGS and is well tolerated.”

https://www.ncbi.nlm.nih.gov/pubmed/30616356

https://journals.sagepub.com/doi/abs/10.1177/1060028018822124?journalCode=aopd

“Why marijuana is headed for the mainstream. The credibility of cannabis as a source of a legitimate pharmaceutical ingredient in prescription medications took a major step forward in 2018 when the FDA approved Epidiolex (cannabidiol) for two types of severe seizures. Epidiolex was a stellar candidate for approval. It reduced convulsive seizures by about 40% and has a good safety profile.”  https://www.ncbi.nlm.nih.gov/pubmed/30620324

The protective effects of β-caryophyllene on LPS-induced primary microglia M1/M2 imbalance: A mechanistic evaluation.

Life Sciences

“Neuroinflammation is observed as a routine characterization of neurodegenerative disorders such as dementia, multiple sclerosis (MS) and Alzheimer’s diseases (AD). Scientific evidence propounds both of the neuromodulatory and immunomodulatory effects of CB2 in the immune system. β-Caryophyllene (BCP) is a dietary selective CB2 agonist, which deserves the anti-inflammatory and antioxidant effects at both low and high doses through activation of the CB2 receptor.

METHODS:

In this study, we investigated the protective effects of a broad range concentration of BCP against LPS-induced primary microglia cells inflammation and M1/M2 imbalance and identifying the portion of the involvement of related signaling pathways on BCP effects using pharmacological antagonists of CB2, PPAR-γ, and sphingomyelinase (SMase).

KEY FINDINGS:

The protective effects of BCP on LPS-induced microglia imbalance is provided by the M2 healing phenotype of microglia, releasing the anti-inflammatory (IL-10, Arg-1, and urea) and anti-oxidant (GSH) parameters and reducing the inflammatory (IL-1β, TNF-α, PGE2, iNOS and NO) and oxidative (ROS) biomarkers. Moreover, we showed that BCP exerts its effects through CB2receptors which overproduction of ceramides by SMase at middle to higher concentrations of BCP reduce the protective activity of BCP and results in the activation of the PPAR-γ pathway.

SIGNIFICANCE:

In conclusion, the low concentration of BCP has higher selective anti-inflammatory effects rather than high levels. On this occasion, BCP by modulating the microglia is able to have potential therapeutic effects in neuro-inflammation conditions and microglia cells such as MS and AD.”

https://www.ncbi.nlm.nih.gov/pubmed/30620895

https://www.sciencedirect.com/science/article/abs/pii/S0024320518308610?via%3Dihub

“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

The effects of cannabinoids on the endocrine system.

“Cannabinoids are the derivatives of the cannabis plant, the most potent bioactive component of which is tetrahydrocannabinol (THC). The most commonly used drugs containing cannabinoids are marijuana, hashish, and hashish oil.

These compounds exert their effects via interaction with the cannabinoid receptors CB1 and CB2. Type 1 receptors (CB1) are localised mostly in the central nervous system and in the adipose tissue and many visceral organs, including most endocrine organs. Type 2 cannabinoid receptors (CB2) are positioned in the peripheral nervous system (peripheral nerve endings) and on the surface of the immune system cells.

Recently, more and more attention has been paid to the role that endogenous ligands play for these receptors, as well as to the role of the receptors themselves. So far, endogenous cannabinoids have been confirmed to participate in the regulation of food intake and energy homeostasis of the body, and have a significant impact on the endocrine system, including the activity of the pituitary gland, adrenal cortex, thyroid gland, pancreas, and gonads.

Interrelations between the endocannabinoid system and the activity of the endocrine system may be a therapeutic target for a number of drugs that have been proved effective in the treatment of infertility, obesity, diabetes, and even prevention of diseases associated with the cardiovascular system.”

Acute Pharmacokinetic Profile of Smoked and Vaporized Cannabis in Human Blood and Oral Fluid.

Image result for journal of analytical toxicology

“Currently, an unprecedented number of individuals can legally access cannabis.

Vaporization is increasingly popular as a method to self-administer cannabis, partly due to perception of reduced harm compared with smoking. Few controlled laboratory studies of cannabis have used vaporization as a delivery method or evaluated the acute effects of cannabis among infrequent cannabis users.

This study compared the concentrations of cannabinoids in whole blood and oral fluid after administration of smoked and vaporized cannabis in healthy adults who were infrequent users of cannabis.

Vaporization appears to be a more efficient method of delivery compared with smoking.”

https://www.ncbi.nlm.nih.gov/pubmed/30615181

https://academic.oup.com/jat/advance-article-abstract/doi/10.1093/jat/bky104/5274655?redirectedFrom=fulltext

Successful cannabis derivatives oromucosal spray therapy for a seronegative stiff-person syndrome: a case report.

 

Image result for bmj journals

“Stiff-person syndrome (SPS) is an uncommon and disabling disorder characterised by progressive rigidity and episodic painful spasms involving axial and limb musculature.

The authors report a patient with seronegative SPS successfully treated with THC-CBD oromucosal spray.

In conclusion cannabinoids can be a therapeutic option to treat spasticity associated with neurological diseases such as stiff-person syndrome.

Our patient’s quality of life has improved remarkably although more information is needed about this particular use.”

https://ejhp.bmj.com/content/19/2/219.2?fbclid=IwAR0PVg0GRQDmu_tXu_vYJmmKHo2MGnJ_EsnkdsR4HE7deFVUtqhAxziHQBc

http://dx.doi.org/10.1136/ejhpharm-2012-000074.352

A Review of Herbal Therapy in Multiple Sclerosis

Logo of advpharmbull

“Medicinal plants have opened a new horizon in curing neurodegenerative disorders such as Parkinson’s disease, AD and MS. literature data review indicated that herbal medicines could be effective in the treatment of MS disease and itsʼ related symptoms, by reducing the demyelination, improving remyelination and suppressing the inflammation in the CNS. On the basis of the above mentioned review, it can be concluded that the anti-inflammatory effect is the main reason of medicinal plants therapeutic effects in MS disease, through which medicinal plants ameliorate the severity of disease and reduce neuropathological changes. In addition to neuroprotective effect, medicinal plants have other beneficial effects for MS patients, such as sedation, improving sleep quality, anti-depressant effects, relief muscle stiffness and reducing bladder disturbance. The medicinal plants and their derivatives; Ginkgo biloba, Zingiber officinale, Curcuma longa, Hypericum perforatum, Valeriana officinalis, Vaccinium macrocarpon, Nigella sativa,Piper methysticum, Crocus sativus, Panax ginseng, Boswellia papyrifera, Vitis vinifera, Gastrodia elata, Camellia sinensis, Oenothera biennis, MS14 and Cannabis sativa have been informed to have several therapeutic effects in MS patients.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311642/

https://www.ncbi.nlm.nih.gov/pubmed/30607330

Adenosine A2A-Cannabinoid CB1 Receptor Heteromers in the Hippocampus: Cannabidiol Blunts Δ9-Tetrahydrocannabinol-Induced Cognitive Impairment

“At present, clinical interest in the plant-derived cannabinoid compound cannabidiol (CBD) is rising exponentially, since it displays multiple therapeutic properties. In addition, CBD can counteract the undesirable effects of the psychoactive cannabinoid Δ9-tetrahydrocannabinol (Δ9-THC) that hinder clinical development of cannabis-based therapies. Here, by combining in vivo and complementary molecular techniques, we demonstrate for the first time that CBD blunts the Δ9-THC-induced cognitive impairment in an adenosine A2A receptor (A2AR)-dependent manner. Overall, these data provide new evidence regarding the mechanisms of action of CBD and the nature of A2AR-CB1R interactions in the brain.”