close of the 28th annual summer cme meeting we …eth∙icˈethik/noun plural noun: ethics a set of...

Lectures & Workshops Objectives8:30 - 10:00amPanel Discussion

Marijuana and MedicineNick M. Spirtos, MD, Beth Schwartz,

and Oscar HuntApproved for 1.5 Prescribed CME

1) Panel discussion addressing medical marijuana in Nevada 2) Discuss safety and potency testing for Nevada's medical marijuana 3) Review medical marijuana research 4) Marijuana regulations in Nevada

10:00 - 11:30amLecture/Brunch

AAFP Journal Jeopardy!Jeffrey Ng, MD, FAAFP

Approved for 1.5 Prescribed CME

1) Join in an interactive round of Jeopardy discussing the latest topics presented in our AAFP Journals

SUNDAY, July 30, 2017 -- 3.0 total CMEDaily Chairs: Thomas J. Hunt, MD, FAAFP and Jeffrey Ng, MD, FAAFP

Close of the 28th Annual Summer CME Meeting

WE HOPE TO SEE YOU NEXT YEAR!!!

Nevada Academy of Family Physicians 28th Annual Summer CME Meeting

July 28–30, 2017

Nevada Academy of Family Physicians • 705 Tahoe St., Ste. A, Reno, NV 89509 775-826-5100 • www.NVAFP.com

NOTES


July 28–30, 2017


Marijuana and Medicine

Presented by: Nick M. Spirtos, MD, Beth Schwartz,

and Oscar Hunt


Sunday, July 30, 2017 8:30—10:00am


July 28–30, 2017


NOTES

"The Chemistry of Cannabis: Reefer Madness or Nobel Prize? "The Apothecary Shoppe”

Nevada Academy of Family Physicians July 30, 2017

Las Vegas, Nevada

Nick M. Spirtos, M.D. Medical Director, Women’s Cancer Center of Nevada

President, Medical Marijuana of Las Vegas, Inc. and Nevada Medical Marijuana Dispensary, Inc. dba

The Apothecary Shoppe

eth∙icˈeTHik/noun plural noun: ethics a set of moral principles, especially ones relating to or affirming a specified group, field, or form of conduct. "the puritan ethic was being replaced by the hedonist ethic"Origin ‐ late Middle English (denoting ethics or moral philosophy; also used attributively): from Old French éthique, from Latin ethice, from Greek ( hē) ēthikē (tekhnē ) ‘(the science of) morals,’ based on ēthos.

Definition and Origin

Definition of Medicinal

• me∙dic∙i∙nalməˈdisənl/adjective adjective: medicinal

1. (of a substance or plant) having healing properties."medicinal herbs"synonyms: curative, healing, remedial, therapeutic, restorative, corrective, health‐giving; medical "an infusion of medicinal herbs"

• relating to or involving medicines or drugs.noun: medicinal; plural noun: medicinals

Requirements for Ethical Prescribing

• MD or DO provides verification of patient evaluation and the presence of a condition identified in the NRS 453A

• Knowledge of the Medicine being prescribed • Familiarity and Understanding of the Literature • Understanding of the metabolism • Associated side effects and drug interactions • Well‐trained staff • Truth in advertising

MD or DO Evaluation

• Generally requires a patient visit and a limited examination

• Thorough medical history, including psychiatric history

• Review of current medications

MD or DO Requirements

• Mobile vans; picking up patients for “skype” (sp?) visits with a “physician” does not in my opinion pass the sniff test

• Ultimately this industry will need to gain the trust of both government agencies and more importantly the patients

Components of Cannabis

• THC • CBD • Terpenes

Pain Studies: Feasibility Trial

• Chronic Pain Patients • Not currently using Cannabis • Weekly Pill Counts

Preliminary Results

• 12 patients • 10 reduced opiate intake by pill count by 50% • 1 No change • 1 Failure

Public safety

Testing and the Public

Terpenoid Profile Cannabis Profile ‐THC

• Delta 9 THCA • Delta 9 THC • Delta 8 THC • THCV • CBD • CBDV • CBG • CBGA, CBC, CBN

Review of the Literature vs. Claims Made

Truths

• GWPharma ‐ The first Phase 3 trial is a placebo‐controlled trial of Epidiolex (CBD at a dose of 20 mg/kg) over a 14 week treatment period and has randomized 171 patients.

• Reduced seizures by 39% vs 13% (placebo)

Truths?

• Many research results and case studies display the beneficial medical effects that medical cannabis provides. Although research on medical marijuana benefits is still limited for many conditions due to strict federal regulations, preliminary results are promising. As research progresses, medical cannabis dispensaries in Las Vegas and across the country will become more accessible to those who benefit from medical marijuana.

Truths ? (continued)

• ….medical cannabis dispensary, and other medical cannabis dispensaries, provide medical cannabis specific to the debilitating symptoms of many common conditions. The following is a list of conditions in which medical marijuana is known to provide the most relief and medical benefit. Select a common condition to see its symptoms and which medical marijuana strains are most beneficial for the symptoms and condition.

Anorexia • Patients suffering from anorexia due to cancer, or even

HIV/AIDS, will significantly benefit from using marijuana as an appetite stimulant. The best method of ingestion for patients dealing with anorexia is usually smoking or vaporizing. Not only does this method of consumption provide the quickest appetite stimulation, but it is also easier to take than edibles. Before they start feeling relief or appetite stimulation, medical marijuana patients may find it hard for some patients to take edibles. Vaporizing is known to be healthier than smoking, which is why many professionals will suggest vaporizing with a condition like this wherein some patients may already be experiencing a severe decrease in their health.

Dementia/Alzheimer’s • Best method of ingestion for this condition:

Research on medical marijuana treatment of Alzheimer’s is still preliminary, but early results show that THC can be extremely effective in fighting the symptoms of Alzheimer’s. Some researchers are saying that THC, a chemical found in marijuana, can slow or even stop the progression of the disease. In fact, research has found that THC fights the formation of brain plaques that form in the brains of Alzheimer’s patients. One study even found that THC is more effective at stopping this plaque from forming than other known inhibitors found in current in Alzheimer’s drugs. There is currently no known best method of consumption for patients with Alzheimer’s. However, numerous studies have been done with patients with Alzheimer’s smoking or vaporizing weed to help fight off the progressiveness of the disease.

Dementia/Alzheimer’s

• Objective: To determine from the available research if cannabinoids are clinically effective in the treatment of dementia

• Selection Criteria: all double and single blind trials assessing the efficacy of cannabinoids at any dose in the treatment of dementia


• Conclusion: There is no evidence that cannabinoids are effective in the improvement of disturbed behavior or in the treatment of the other symptoms of dementia.


• Cochrane Database Syst Rev. 2009 Apr 15;(2) • Cannabinoids for the treatment of dementia. • Krishnan S1, Cairns R, Howard R.


• One Study

Cancer • Research on medical marijuana use for treating cancer

symptoms has been progressing. Some studies have shown that smoked or vaporized marijuana is helpful for treating the neuropathic pain that can be associated with cancer. Vaporized marijuana may also help some patients increase their appetite or help them keep food down when going through cancer treatment. In taking marijuana concentrates has also shown to help people with pain management, requiring medical marijuana patients to take less pain medication. Most recently, some research has shown that THC and other cannabinoids, such as CBD, can actually help slow the growth rate and/or cause death in certain types of cancer cells. More research needs to be done before there can be conclusive results, however.

Cancer

• Oncol Rep. 2007 Apr;17(4):813‐6.Endocannabinoids as emerging suppressors of angiogenesis and tumor invasion (review).Bifulco M1, Laezza C, Gazzerro P, Pentimalli F.

• The potential use of cannabinoids to retard tumor growth and spreading is even more appealing considering that they show a good safety profile, regarding toxicity, and are already used in cancer patients as palliatives to stimulate appetite and to prevent devastating effects such as nausea, vomiting and pain.

Anti‐angiogenesis effects on cancer

• Multiple randomized studies demonstrating no increase in overall survival

• At best slight increase in progression free interval

• Failed in breast cancer and barely surviving in ovarian cancer patients.

Pain • J Pain. 2013 Feb;14(2):136‐48 • Low‐dose vaporized cannabis significantly improves

neuropathic pain.Wilsey B1, Marcotte T, Deutsch R, Gouaux B, Sakai S, Donaghe H.

• The analgesia obtained from a low dose of delta‐9‐tetrahydrocannabinol (1.29%) in patients, most of whom were experiencing neuropathic pain despite conventional treatments, is a clinically significant outcome

• In general, the effect sizes on cognitive testing were consistent with this minimal dose. As a result, one might not anticipate a significant impact on daily functioning.

Pain‐Reality Check

• Sativex – Trial sponsored by GWPharma fails to reach statistical significance.

• Dosing – 2.7 mg THC and 2.5 mg CBD…too low?

Nausea and Vomiting

• Check it out • How many of you believe there is a positive effect of cannabis on patients suffering from these symptoms?

Post‐Anesthesia Nausea and Vomiting (PONV)

• Anesth Analg. 2015 Nov;121(5):1157‐64. • Intravenous Delta‐9‐Tetrahydrocannabinol to Prevent

Postoperative Nausea and Vomiting: A Randomized Controlled Trial.Kleine‐Brueggeney M1, Greif R, Brenneisen R, Urwyler N, Stueber F, Theiler LG.

• .125mg/kg THC • The study was discontinued after 40 patients because of the

inefficacy of THC against PONV • CONCLUSIONS:

Because of an unacceptable side effect profile and uncertain antiemetic effects, IV THC administered at the end of surgery before emergence from anesthesia cannot be recommended for the prevention of PONV in high‐risk patients.

Chemotherapy Induced Nausea and Vomiting (CINV)

• Trials using Marinol‐like products • Efficacy, tolerability, and safety of cannabinoids for chemotherapy‐induced nausea and vomiting‐a systematic review of systematic reviews.Tafelski S1, Häuser W2,3, Schäfer M4.

• Schmerz. 2016 Feb;30(1):14‐24. • Due to the lack of RCT data and safety concerns, herbal cannabis cannot be recommended for CINV.

How do we responsibly respond to these results?

• Insist we are right and the studies were wrong?

• Conduct better designed trials with different combinations (strains and doses)

Chemotherapy Induced Nausea and Vomiting (CINV)

• Randomized Double‐Blinded; Placebo Controlled trial with crossover using Syrup of THC/CBD developed by the Apothecary Shoppe

• 152 patients with null hypothesis – there will not be a 30 % reduction in grade 2 or greater nausea and vomiting in patients receiving moderately ematogenic chemotherapeutic regimens

Recommendations

• Physicians and staff in explaining potential benefits make a special effort to make it clear that our knowledge for the most part is anecdotal and much more work is required

• Instruct staff not to make statements that can not be supported by the literature

Terpenoid Profile

Terpenes

• Hydrocarbon • Responsible for fragrance of many plants

Terpenes‐ Facts vs Claims • Myrcene • HopsMyrcene is the most common terpene in marijuana strains (up to 60% of the essential oils of certain varieties) however, it is not found in hemp textiles. It is also found in large quantities in hops or in the West Indian wood (Saint Thomas Bay). Its smell is very similar to cloves (girofle). Myrcene is a potent analgesic, anti‐inflammatory and antibiotic. It blocks the action of cytochrome, aflatoxin B, and other pro‐mutagenic carcinogens. It also has a relaxing, calming, anti spasmodic and sedative effect. Acting in synergy with THC, myrcene increases its psychoactive potential.

Terpenes‐ Facts vs Claims • Limonene • Limonene is often the second, third or fourth terpene found in

cannabis resin. This family of terpenes produces the typical smell we all recognise as citrus. Limonene has anti fungal and anti bacterial properties and is also antiCitricscarcinogenic. It prevents the detioration of the RAS gene, one of the factors that contribute to the development of tumors. It also protects against Aspergillus and carcinogens present in smoke. Limonene quickly and easily penetrates the blood‐brain barrier, which increases systolic pressure. During testing on the effects of limonene, participants experienced an increase in attention, mental focus, well‐being and even sex drive. Limonene is used sometimes in spray form, to treat depression and anxiety. It also has the effect of reducing the unpleasantness of gastric acid and stimulates the immune system. Plants use limonenes to ward off predators; for example, it repells flies like any insecticide.

Terpenes‐ Facts vs Claims

• Caryophyllene • Caryophyllene can be found in various herbs and spices, particularly in black pepper, which contributes to the spicy flavour. It is a local anti inflammatory and analgesic, and one of the active ingredients of the clove (Giroflé). It is a black pepper efficient remedy to relieve toothache. It also has anti fungal properties. This terpene has the particularity of selectively activate the cannabinoid 2 receptors (CB2), while it is not a cannabinoid. This discovery opens the door to many possibilities in medicinal research.

Terpenes‐ Facts vs Claims • Pinene • Pinene is responsible for the familiar smell associated with pine and fir trees, and

to be more precise, its resin. It is the main ingredient of the essence of turpentine. It is present also in many plants such as Sage or Rosemary. Pinene is used in medicine as an expectorant, bronchodilator, anti inflammatory and local antiseptic. It also crosses the blood‐brain barrier very easily, where it acts as an inhibitor of acetylcolynesterases, preventing the destruction of molecules responsible for the transmission of information, which results in memory improvement. It is largely due to the presence of pinenes that Rosemary and Sage have been considered to be beneficial plants during thousands of years of traditional medicine. This terpene can, in part, counteract the effects of THC, which leads to a decrease in the acetylcholine levels. The result is that the memory fails more with pure THC than with THC mixed with pinene. Skunk strains are, for example, recognized for their high levels of pinenes. Because this produces a bronco dilator effect, the smoke of plants rich in pinene give the sensation of sucking more air, which can cause hyperventilation or sometimes cough. Pinene also improves concentration, personal satisfaction and energy, but it may be limited by the effects of the terpinol.


• Terpineol • Terpineol smells of lilac, crabapple blossoms and lime blossoms. During tests on mice, their mobility was reduced to 45%. This explains the sedative effect of some marijuana strains. Terpineol is often found in strains that have a high level of pinenes, the aromas of which can hide the smell of terpineol.


• Linalool has a floral smell like lavender and spring flowers. Humans are able to smell it at very low levels, from 1 PPM in air. Linalool is currently used in the treatment of various cancers. It also has a powerful calming action, anti anxiety, and produces a sedative effect. In tests on mice it was discovered that their activity decreased by 75%. Linalool is thus partly responsible for the sedative effects of certain marijuana strains. It also has analgesic and anti‐epileptic properties.


• Eucalyptol • Eucalyptol (also called 1,8‐cineol) is the main ingredient of eucalyptus essential oil. It has the characteristic Eucalyptus leaf, minty smell of this tree, and is also found in small amounts in marijuana. Its effects relieve pain and improve concentration and inner balance. Plants containing eucalyptol enhance meditation and concentration.

Terpenes‐ Facts vs Claims • Other terpenes that can be found in marijuana resin are, for example, phellandrene, phytol, humulene, pulegone, bergamotene, farnesene, D3‐carene, elemene, fenchol, aromadendrene, bisabolene, and many more…We see then that the endless possibilities of terpene profiles are responsible for variations in taste and effects of marijuana. Some combinations of terpenes can act in synergy (the effects are added), while others are antagonists (the effects inhibit each other). Some terpenes increase the assimilation of THC, while others affect the flow of dopamine and serotonin, two of the main regulators of mood and behavior.

Terpenoid Profile

• Z Naturforsch C. 2011 Jul‐Aug;66(7‐8):353‐9. • Pharmacological activity of (R)‐(+)‐pulegone, a chemical constituent of essential oils.de Sousa DP1, Nóbrega FF, de Lima MR, de Almeida RN.

• (R)‐(+)‐Pulegone caused a significant decrease in ambulation and an increase in pentobarbital‐induced sleeping time in mice, indicating a central depressant effect.

• These results suggest that (R)‐(+)‐pulegone is a psychoactive compound and has the profile of an analgesic drug.

Recommendations regarding terpenes

• Even more important to recognize the scant literature

• Interactions between THC and CBD are just beginning to be understood

• There are over 200 identified terpenes in cannabis so drawing broad conclusions about them is virtually impossible

• Observation of elderly vs younger patient

Metabolism and Drug to Drug Interactions

• Cytochrome 450 pathway • Difficult to predict effects on individual patients

• Most important is the education provided to the staff

• Staff must have basic understanding of the most problematic drugs and must be trained to ask patients what other medications they are taking…anything less is irresponsible

Truth in Advertising – just for fun Delivery

• Nevada medical marijuana law allows for reciprocity, meaning that medical marijuana patients visiting from any state can legally purchase from Las Vegas dispensaries! We can even deliver your medicine straight to your hotel room:

Conclusions

• The importance of how this industry is perceived and nourished in its infancy cannot be overstated

• If our credibility is to be lost over bus services that as a group we should have taken a stand, then shame on us

• And if already we are more concerned about patients’ getting their fixes, buzzes, and all‐day highs then we should not be surprised if the Division strictly interprets every statute in order to put the brakes on a potentially dangerous careening car before we have a significant accident

Safety and Potency Testing for Cannabis in Nevada

THE WHAT AND WHY OF NEVADA’S TESTING LABORATORIES OSCAR HUNT, BS FIELD CHEMIST, CLIENT RELATIONS

Objectives Describe the sampling requirements for lot

testing in Nevada Discuss bioactive components found in

cannabis Review the stringent testing requirements

for cannabis in Nevada

Cannabis as Medicine Medicinal plant that has been used for thousands of years Due to federal drug classification, very little scientific study has

been done to understand this plant’s medicinal qualities 26 states and counting have some form of legal cannabis Qualifying conditions in Nevada:

AIDS Cancer Glaucoma PTSD Cachexia Muscle Spasms and MS Seizures Nausea Severe Pain

Pharma

Cannabis is gaining major mainstream popularity as a replacement for some pharmaceuticals.

Pharmaceutical companies are beginning to manufacture cannabis based medications The only product currently FDA approved (1985) treats

nausea, vomiting and weight loss (dronabinol) Others are currently being developed

Lot Testing

Nevada requires a seed to sale inventory system that tracks every gram of product that is produced

Every 5 pounds of dry flower must undergo and pass testing to be eligible for sale. Other product types have different maximum lot sizes

A lab testing agent goes to the facility to sample the lot and bring the sample back to the lab for analysis

Potency Determined by the interplay of the bioactive compounds and

consist of: Cannabinoids-Psychoactive and non psychoactive compounds found

in cannabis

Terpenes-Naturally occurring aromatic molecules that contribute to cannabis’s unique scents and flavors

Cannabinoids Tertrahydrocannabinol, THC is the most common metric to gauge

the potency of a product Up to 30% by dry weight in flowers

Cannabidiol, CBD is also well known to have medicinal qualities Non-psychoactive

Cannabinol, CBN has been shown to be a powerful sleep aid Cannabichromine, CBC shows promise as an anti-inflammatory Tetrahydrocannabivarin, THCV energy stimulation and appetite

suppression Cannabigerol, CBG has many potential medical uses

Terpenes Myrcene- anti inflammatory, calming, sedative (thyme, bay leaf) Limonene- antifungal, uplifts mood and attitude (citrus fruit) Humulene- anti tumor, anti bacterial, appetite suppressant (hops) Pinene- anti inflammatory, bronchodilator (pine and fir needles) B-caryophyllene- antioxidant, anti inflammatory (black pepper,

cloves) Linalool- calming, relaxing, sleep aid (lavender)

All of these terpenes have many more suspected heath benefits. Ongoing studies are determining all of the possible uses of these compounds

Entourage effect Interplay of active compounds in cannabis. The presence of one

compound can increase the effects of another. Myrcene can aid THC in crossing the blood brain barrier and helps THC

bind to CB1 receptors more efficiently

Limonene can increase the skins ability to absorb and uptake cannabinoids by 10x

*Ensemble effect- the importance of THC has diminished and many now believe all compounds are equally important thus forming an ensemble of all compounds rather than an entourage the support THC

Safety

Visual inspection for foreign matter Microbial growth Heavy Metal Pesticide Mycotoxin Moisture Residual Solvents

Visual Inspection Checks for hair, dirt, plastic, bugs, mold, powdery mildew

or any other foreign matter.

Microbial Growth

Microbial plating is used to detect the presence of: Yeast and Mold Aerobic bacteria Enterobacteria E. coli

Heavy Metals

Lead Mercury Arsenic Cadmium

Pesticides State Approved Pesticides and

Allowable Limit: Abamectin 0.05PPM Acequinocyl 4PPM Bifenazate 15PPM Bifenthrin 0.05PPM Captan 0.05PPM Cyfluthrin and beta-cyfluthrin 4PPM Cypermethrin 0.05PPM Daminozide 0.05PPM Dimethomorph 60PPM Etoxazole 7PPM Fenhexamid 30PPM Flonicamid 7PPM

Fludioxonil 0.02PPM Imidacloprid 0.05PPM Myclobutanil 9PPM Paclobutrazol 0.05PPM Pentachloronitrobenzene

(quintozene) 0.2PPM Piperonyl Butoxide 2PPM Pyrethrin 1PPM Spinetoram 1.7PPM Spinosad 1.7PPM Spirotetramat 10PPM Thiamethoxam 0.02PPM Trifloxystrobin 11

Mycotoxin

Mycotoxins are a byproduct of the metabolism of certain species of Aspergillus molds. Aflatoxin (known carcinogen) Okratoxin (suspected carcinogen)

Maximum allowable limit is 20ppb

Moisture

Maximum moisture level of 15% is allowed on dried flower. Higher levels of moisture can promote growth of mold.

Residual solvents

For solvent based extracts only Propane, butane, and ethanol are

the three most commonly used

Questions?


July 28–30, 2017


NOTES


July 28–30, 2017


AAFP Journal Jeopardy!

Presented by: Jeffrey Ng, MD, FAAFP


Visit nvafp.com for any available handouts

Sunday, July 30, 2017 10:00—11:30am


July 28–30, 2017


NOTES

close of the 28th annual summer cme meeting we …eth∙icˈethik/noun plural noun: ethics a set of...

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