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Medical Cannabis &

the Advanced Practice Nurse

Presented by

Caroline Coussens, APRN-CNS, BC

Stephanie Moore, DNP, APRN, ACNS-BC

Objectives

• Define cannabinoids for medical use

• Identify the role of the Advanced Practice Nurse in

cannabinoids for medical use

• Describe the current legislative initiatives in Oklahoma related

to medical cannabis/marijuana

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Definition of Medical Marijuana (MM)

• Medical Marijuana refers “to using the whole,

unprocessed marijuana plant or its basic extracts to

treat symptoms of illness and other conditions”.

National Institute on Drug Abuse (NIDA), 2017

Marijuana • Marijuana refers to the dried leaves, flowers, stems, and seeds from the plant genus

cannabis

• Cannabis is 3 different plants– Cannabis indica

– Cannabis sativa

– Cannabis ruderalis

• Most commonly used illicit drug in the United States and world

• Other names for marijuana are: ganja, grass, hashish, hemp, Indian hemp, marijuana, pot, reefer, weed, herb, bud, Mary Jane

• FDA - Schedule 1 Drug

NIDA, 2017 & Bridgeman & Abazia, 2017

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Marijuana Cont.

• Marijuana contains more than 500 chemicals

• Marijuana also contains more than 100 compounds called

cannabinoids

– Two main cannabinoids of interest are:

• Cannabidiol (CBD)

• Delta-9-Tetrahydrocannabinol (THC)

NIDA, (2018).

Methods of Administration

• Inhalation via smoking – most common

• Inhalation via vaporization – becoming increasingly more common

• “Dabbing” – flash vaporizing

• Ingestion of edible products

– Eaten (brownies, cookies, candy)

– Drank (brewed as a tea)

– Sublingual tincturesNIDA, 2018

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Pharmacokinetics

• Pharmacokinetic research challenging

• Cannabinoid components vary greatly

• Absorption and onset of action vary

– Depending on route of administration

– Ratio of THC-to-CBD in a product

Bridgeman & Abazia, 2017

Drug Schedules: A Review

• Classified into five (5) distinct categories or schedules

• Classification is dependent on:

– The drug’s acceptable medical use

– The drug’s abuse or dependency potential

• Abuse rate is a determinate factor in the scheduling of the drug

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Schedule 1 Drugs, Chemicals, Substances

• High potential for abuse

• Potential to create severe psychological and/or physical dependence

• Drugs with no currently accepted medical use

• Examples include – Heroin– Lysergic acid diethylamide (LSD)

– Marijuana (cannabis)

– 3,4-methylenedioxymethamphetamine (ecstasy)

– Methaqualone

– Peyote

Drug Enforcement Administration (DEA), 2016

Federal Law

• Marijuana is a Schedule 1 substance

• Marijuana is illegal to use, possess, cultivate, or distribute

• State marijuana laws cannot preempt (overrule) federal law

• Federal marijuana laws:

– Laws that the federal government enacts to criminalize marijuana

possession, sale, and cultivation

DEA, 2016

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Varieties of Cannabinoids

1. Phytocannabinoids – genus cannabis plant (THC and CBD)

2. Endocannabinoids – natural endogenous cannabinoids are A-

AG and anandamide

3. Synthetic – marinol (dronabinol), Syndros, Epidiolex

Phytocannabinoids

CBD & THC

Cannabidiol or CBD• Lacks intoxicating properties

• Agonist of serotonin 5-HT1A receptors

• Enhances adenosine receptor signaling suggesting potential therapeutic role pain & inflammation

• CBD has potential for symptom relief

– reducing muscle spasms

– controlling epileptic seizures

– Anxiety

– Movement disorders

– Multiple sclerosis

NIDA, (2018)

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Phytocannabinoids

CBD & THC

Tetrahydrocannabinol

• Marijuana’s main mind-altering

ingredient – ‘high’

• May increase appetite & reduce

nausea

• May also decrease pain, inflammation

• May be useful in muscle control

problems

• May alleviate depression, headaches,

including migraines

NIDA, (2018)

Endocannabinoids

The Reward Circuit:

How the Brain responds to Marijuana

www.youtube.com/watch?v=s27f7Jzy2k0#action=share

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The Human Endocannabinoid System

• Largest receptor system in the body

• Human body makes Cannabis-like substances (endogenous cannabinoids)– Created on demand; not stored

– A-AG and anandamide

– These interact with ECS receptors – CB1 and CB2

– Cannabinoid receptors react to and are activated by exogenous cannabinoids

• Helps maintain homeostasis throughout the entire body– “eat, sleep, relax, forget, and protect”

• Cannabinoids are involved in immune function

• If endocannabinoid deficient – more likely to become sick

• ECS still not well understoodPettinato, 2017; Pirschel, 2018

Endocannabinoids (eCBS)

• Endocannabinoids and their receptors found throughout body

– Nervous system

– Internal organs

– Connective tissues

– Glands

– Immune cells

• Play a role in the pathology of many disorders

• Also serve a protective functionBridgeman & Abazia, 2017

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Optimal Functioning of ECS

• Exercising

• Reducing stress

• Manipulating our diets

• Omega-3 fatty acids in balance with omega-6 fatty acids

• Caryophyllene (an essential oil)

• Flavonoids

• Yoga or meditation

• Acupuncture or osteopathic treatments

Bridgeman & Abazia, 2017

Synthetic Version of Marijuana

FDA Approved

• Marinol (dronabinol), Syndros (dronabinol)

– Schedule III

– Dronabinol is a synthetic delta-9-THC

– Indications:

• anorexia/weight loss related to AIDS: 2.5mg BID; Max 20mg/day

• Chemo-related nausea/vomiting: 2.5mg BID; Max 16.8mg/day

– Adverse Reactions: dizziness, confusion, euphoria, depression or

seizures, tachycardia, abdominal pain

– Drug interactions: warfarin, metronidazole, CNS depressantsFDA, 2015

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Synthetic Medications Cont.

• Cesamet (nabilone)

– Schedule II

– Synthetic

• Chemical structure similar to THC

– Indications:

• Nausea/vomiting related to chemotherapy

– Dosage: 1-2mg BID; Max dosage 2mg TID

– Adverse Reactions: drowsiness, dizziness, dry mouth, euphoria, lack of coordination, headache, difficulties in concentrating; tachycardia, hallucinations, hypotension

UpToDate, 2019

Synthetic Medications Cont.

• Epidiolex– Schedule V

– First cannabis-derived prescription medicine available in the United States

– Active ingredient – cannabidiol; does not contain THC

– Indications: Treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients 2 years of age and older

– Adverse Reactions: hepatocellular Injury, somnolence & sedation, suicidal behavior & ideation

– Hypersensitivity reactions: withdrawal of antiepileptic drugs

– No data on developmental risks associated with use during pregnancy

UpToDate, 2019

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Epidiolex Dosing

Challenges of MM and Synthetic Formations

• There is limited evidence comparing the MM and synthetic

forms

• MM is derived from an entire plant

• Synthetics focus on 1 or 2 cannabinoids

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Synthetic Cannabinoids (K2/Spice)• Human-made mind-altering chemicals sprayed on dried, shredded plant material or

vaporized to produce a high. The chemicals are similar to chemicals found in the marijuana plant

• Act on the same brain cell receptors as THC

• Smoked, used in E-cigarettes, brewed as a tea, mixed with marijuana

• Effects can be unpredictable & severe or life-threatening

• Effects reported by users: elevated mood, relaxation, altered perception, symptoms of psychosis

• Can also cause serious mental & physical health problems including: – Tachycardia

– Vomiting

– Violent behavior

– Suicidal thoughts

• Synthetic cannabinoids can be addictive

• Standard drug tests cannot detect the chemicals found in synthetic cannabinoids

NIDA, 2018

Beer Makers

• Beer makers investing in cannabis companies

• Molson Coors is entering a joint venture with The HydropothecaryCorporation, a Canadian marijuana producer, to make non-alcoholic cannabis-infused beverages

• Heineken is betting on a brew made with marijuana instead of alcohol, and it could help give a boost to the struggling beer industry

• Anheuser-Busch is partnering with medical cannabis company Tilray in a $100 million deal to research cannabis-infused drinks for the Canadian market

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FDA Supports Sound Scientific Research

• Study of marijuana in clinical settings is needed to assess the

safety and effectiveness of marijuana for medical use

• To date, FDA has not approved a marketing application for a

drug product containing or derived from botanical marijuana

• Collaboration with other agencies involved in marijuana

research

– National Institute on Drug Abuse (NIDA)

• Responsible for overseeing the cultivation of marijuana for research

• Marijuana of varying potencies & compositions are available

• Farms are contracted out for these purposes.

Risks related to Medical Marijuana

• Physiological

– Acute

– Chronic

• Dependence

– Gateway drug

• Do No Harm

– Alleviation of particular symptoms versus degree of harm associated

with use

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Short Term Adverse Effects of Marijuana on Brain

• Altered senses

• Altered sense of time

• Changes in mood

• Impaired body movement

• Difficulty with thinking and problem-solving

• Impaired short-term memory and concentration

• Hallucinations (when taken in high doses)Whiting et al, 2015

Short Term Adverse Effects Cont.

• Delusions and paranoia (when taken in high doses of THC)

• Psychosis (when taken in high doses of THC)

• Dry mouth

• Fatigue

• Somnolence

• Confusion

• Dizziness

• Increased Heart rate

• Increased risk of heart attack and stroke

Whiting, et al., 2015

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Long Term Adverse Effects

• ? link to mental illness in some

• Worsening symptoms in patients with schizophrenia

• Addiction – occurs in 10% of users who start smoking marijuana before age 25

• Altered brain development; cognitive impairment; poor educational outcomes

• Chronic bronchitis

• Depression

• Vascular conditions (MI, stroke, TIA’s)

Bridgeman & Abazia, 2017

Whiting, et al., 2015

? Link Between Marijuana Use, Schizophrenia

• Gene identification

– AKT1 gene (Previous research has found a link between the AKT1 gene and people who have gone on to develop psychosis)

– When under the influence of cannabis, young people with variation in the ‘AKT1’ gene experienced visual distortions, paranoia and other psychotic-like symptoms more strongly than young people without this variation.

• Family history of schizophrenia increases the risk among people wh

• Risk of psychotic episodes

• Decrease in the age of schizophrenia onset

Morgan, Freeman, Powell, & Curran, 2016

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? Link between Marijuana use and psychiatric

disorders• Studies link marijuana use to increased risk for psychiatric disorders:

– Psychosis (schizophrenia)

– Depression

– Anxiety

– Substance use disorders

• Variables include:– Amount of drug used

– Age at first use

– Genetic vulnerability

• NIDA. (2018, June 25). Marijuana. Retrieved from https://www.drugabuse.gov/publications/research-reports/marijuana on 2019, March 2

Cannabinoid Hyperemesis Syndrome

• Cause – chronic marijuana use

– Nausea/vomiting receptors “turned off” and overstimulated

• Three phases:

– prodromal

– hyperemetic (usually 48 hours)

– recovery (days, weeks, months)

• Signs/Symptoms:

– nausea/vomiting

– abdominal pain

Galli, Sawaya, & Friedenberg, 2011

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Cannabinoid Hyperemesis Syndrome Cont.

• Treatment: May require hospitalization due to abdominal pain, volume depletion, and severe nausea and vomiting

• Treatment mainly supportive therapy – fluid resuscitation

– anti-emetic medications (does not work well)

– hot showers/baths

– Capsaicin cream

• Cure – stop using

• Unnecessary removal of gallbladders

• Colorado ERs report daily visits due to CHS

Galli, Sawaya, & Friedenberg, 2011,

Teens

• Marijuana has a more damaging effect on teenagers’ long-term cognitive abilities than alcohol

• Cognition did not improve after stopping

• Frequent marijuana use:

– Lower scores on tests of memory

– Difficulty with learning new information and higher level thinking that involves problem solving and processing information

• Teens who smoke daily are:

– 60% less likely to graduate high school or college than those who never use

– 7 more times likely to attempt suicide

• Link between marijuana use in adolescence and psychotic symptoms Cerda, Wall, & Feng, 2017; Morin, 2018

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Use of Medical Marijuana in Cancer• Chemotherapy-Induced nausea and vomiting

– Lack of evidence to support use

– Leading to lack of specific guidelines for dosing or safety

– Lack of data on long term effects

– Participants unable to tolerate the smoked marijuana

• Appetite stimulant– Lack of evidence to support use

– Synthetic cannabinoid has shown to improve appetite & promote weight gain

• Chronic pain

Whiting, et al., 2016

Cancer Risk & Use of Medical Marijuana• Moderate evidence of no statistical association between cannabis

smoking & lung cancer

• Moderate evidence of no statistical association between cannabis use and head/neck cancers

• Limited evidence to support an association of cannabis and testicular cancers

• Insufficient evidence to support or refute an association between cannabis & esophageal cancers

• Insufficient evidence to support or refute association between cannabis & prostate, cervical, malignant gliomas, non-Hodgkin lymphoma, penile, anal or bladder cancers

Health Effects, 2017

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Other Health Effects

• Breathing problems (in those who smoke marijuana)

– Higher risk of lung infections & more frequent lung illness

• Cardiac effects

– Increased heart rate

– Increased risk of heart attack and stroke

• Child development during and after pregnancy

• Dizziness

• Dry Mouth

• Negative drug-to-drug interactions

• Abnormal lab values – LFT’s

Bridgeman & Abazia, 2017; Whiting et al., 2015

Controversies related to Medical Marijuana

• Legal, Ethical & Societal Implications

• Safe administration, packaging, and dispensing

• Adverse health consequences and deaths attributed to intoxication

• Therapeutic indications based on limited clinical data

Bridgeman & Abazia, 2017

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Legalized Medical Marijuana

• Individual states:

– Regulate who may use it

– Regulate how the product is distributed within its borders

– Processes in place for certifying and registering eligible people

– Designated dispensaries (medical marijuana centers)

– May vary in the list of conditions that qualify people for treatment

with medical marijuana

Marijuana Legalization 2018 – State by State

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Medical Use of Marijuana

• Appetite Stimulation in HIV/AIDS

• Spasticity due to multiple sclerosis or paraplegia

• Depression

• Anxiety disorder

• Sleep Disorder

Whiting, et al., 2016

Qualifying Conditions (may vary between states)

• ALS

• Anorexia due to HIV/AIDS

• Chronic Pain

• Crohn’s disease

• Epilepsy or seizures

• Glaucoma (not recommended by the American Academy of Ophthalmology)

• MS or severe muscle

spasms

• Nausea, vomiting or

severe wasting associated

with cancer treatment

• Terminal illness

• Tourette syndrome

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Contraindications vs. Precautions with MM

• Contraindications

– Under age 25

– Pregnancy & breast feeding

– Schizophrenia

– Psychosis that occurred with

recreational use

– Compromised cardiac status

– Hx of alcohol or substance abuse

• Precautions

– Driving motor vehicles

– Operating industrial machinery

– Currently using sedatives &

hypnotics

– Hypotension

– Heavy tobacco use

– Taking strong CYP 3A4 inhibitors

(ketoconazole, clarithromycin)

Challenges Facing Cannabis Research

• Schedule 1 research registration must be acquired from the

U.S. Drug Enforcement Administration AND typically a

Schedule 1 research license from the state-controlled drugs

agency.

• Cannabis material MUST BE obtained from the National

Institute on Drug Abuse (NIDA), the sole source of research-

grade cannabis that is federally lawful.

• These requirements can take three to six months.

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Oklahoma Medical Marijuana Authority: OMMA

• Manages the medical marijuana program

• Application processing, licensing, compliance monitoring

• Resides within the Oklahoma State Department of Health

• Under the authority of Commissioner of Health (Tom Bates)

www.omma.ok.gov

OMMA website

• Apply (patients & caregivers, business, growers etc…)

• Find a list of physicians & Locations

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Physicians

Dispensaries

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Current Events in Oklahoma

• Call center closed temporarily February 6 due to a major backlog– 4,000 applications/week late January and early February

– 16 full time employees reviewing applications as of February 6

– Law states that applicants must receive a response from the OMMA within 14 days of application

– As of 2/4/19 – 61,000 people had applied for licenses with 47,000 approved

• Anticipating 40,000-80,000 applications this first year of legalization

Grimwald, Harrison. Tulsa World Feb.6, 2019 License requests ramp up this year. pp.A1,A4

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The Numbers: January-February 2019

Oklahoma Medical Marijuana &

Patient Protection Act

• Signed into law March 14, 2019

• Takes effect 90 days after the Legislature adjourns on May 31

• Grants rule making powers to the OMMA

• Provision allowing employers in ‘safety sensitive’ fields to

inquire if employees have medical marijuana licenses

• For more information:

http://oklegislature.gov/BillInfo.aspx?Bill=hb2612

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Other Bills related to Medical Marijuana

• Bill addressing physician requirements

• Employee protection

• State taxes, revenue surpluses (go toward common education

& substance abuse treatment programs

• Advertising, packaging

Physician Information

• Online form must be submitted

• Licensed and Board Certified

• Bona fide physician patient relationship

• Medical record must be established

• Physician may certify caregivers of patients that are homebound or do not have the capability to self-administer or purchase medical marijuana due to a developmental disability or a physical or cognitive impairment

• More details at omma.ok.gov

OMMA, 2019

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Medical Marijuana Banking Issues

• Federal law: marijuana illegal

• House of Representatives Financial Services Committee proposal

– Secure and Fair Enforcement Banking Act of 2019 (SAFE Banking Act of 2019)

– Protect banks & employees from punishment for providing services to cannabis businesses

• Without banking accounts, businesses operate on a cash basis

• This committee “does not have jurisdiction over descheduling a drug.” (Rep. Blaine Luetkemeyer)

Merle, 2019

Cost for applicants

• Marijuana Doctors: A new kind of healthcare

– https://www.marijuanadoctors.com/medical-marijuana-

doctors/ok/tulsa/restorative-wellness-center-_3636

• Links to assist in finding a physician, cost, etc…

• Examples:

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Medical Facility Position Statements

• Find out the position for your facility

• Many states have passed laws permitting use

• Federal law does not permit legal possession or use of medical

marijuana

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When Identifying Appropriate Patients for MM

• Determining the risks

• Is there a legitimate medical symptom that MM can treat?

• Does the patient have good intentions or are they being

pushed to ask for someone else?

• Does the patient really understand MM?

• There are no dosing recommendations

What Do I Tell my Patients?

• If they are using MM, they need to be educated to include as part of their medication list

• Common side effects – psychomotor & cognitive impairment, fatigue, dizziness, dry mouth, tachycardia, dry eyes

• Hyperemesis syndrome

• Bleeding disorders

• Changes in blood glucose levels

• Potential medication interactions

• Increase risk of respiratory infections

Baileys, 2018

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What Do I tell my Patients Cont.?

• If patients are using MM, they need to be educated to include in discussions with providers – this includes smoking, vaping & edible

• There is a difference between MM and synthetic forms of marijuana

• Caution them on misinformation on the internet

• More research is needed for dosing, medication interactions, & safety

Schulmeister, 2018

Cart before the horse???

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Oklahoma Recreational Marijuana

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ANA Position on use of Medicinal Cannabis

• “It is the shared responsibility of professional nursing organizations to speak for nurses collectively in shaping health care and to promulgate change for the improvement of health and health care” (ANA, 2015, p. 36).

• Therefore, the ANA strongly supports:

– Scientific review of marijuana’s status as a federal Schedule I controlled substance and relisting marijuana as a federal Schedule II controlled substance for purposes of facilitating research

– Development of prescribing standards that includes indications for use, specific dose, route, expected effect and possible side effects, as well as indications for stopping a medication

ANA, 2016

ANA Position Cont.

• Establishing evidence-based standards for the use of marijuana and related cannabinoids

• Protection from criminal or civil penalties for patients using therapeutic marijuana and related cannabinoids as permitted under state laws

• Exemption from criminal prosecution, civil liability, or professional sanctioning, such as loss of licensure or credentialing, for health care practitioners who discuss treatment alternatives concerning marijuana or who prescribe, dispense or administer marijuana in accordance with professional standards and state laws

American Nurses Association (ANA), 2016

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Recommendations from IOM

1. Research should continue into the physiological effects of synthetic and plant-

derived cannabinoids & the natural function of cannabinoids found in the body.

2. Clinical Trials of cannabinoid drugs for symptom management should be

conducted with the goal of developing rapid-onset, reliable, and safe delivery

systems.

3. Psychological effects of cannabinoids such as anxiety, reduction and sedation,

which can influence medical benefits, should be evaluated in clinical trials

4. Studies to define the individual health risks of smoking marijuana should be

conducted, particularly among populations in which marijuana use is prevalent.

IOM, 2017

Recommendations from IOM

5. Clinical trails of marijuana use for medical purposes should be conducted under the

following limited circumstances: trails should involve only short-term marijuana use (less

than 6 months), should be conducted in patients with conditions for which there is

reasonable expectation of efficacy, should be approved by institutional review boards, and

should collect data about efficacy.

6. Short-term use of smoke marijuana (less than 6 months) for patients with debilitated

symptoms (such as intractable pain, or vomiting must meet the following conditions:

-failure of all approved medications to provide pain relief, symptoms can reasonably be

expected to be relieved by rapid-onset cannabinoid drugs,

-such treatment is administer under medical supervision in a manner that allows for

assessment of treatment effectiveness, and involves an oversight strategy comparable to

IRB process that could provide guidance within 24 hours of a submission by a physician to

provide marijuana to a patient for specified use.

IOM, 2017

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New Information

This Photo by Unknown Author is licensed under CC BY-NC-ND

Summary

• Medicinal cannabis is a schedule I controlled substance with

no accepted medicinal use based on research

• Insufficient evidence to support use

• There is a need for more research with medicinal cannabis

to determine benefits and risks

• “A lack of scientific research has resulted in a lack of

information on the health implications of cannabis use”

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Questions?

Resources

• FDA.gov

• National Institute on Drug Abuse

https://www.drugabuse.gov/drugs-abuse/marijuana

• Oklahoma Medical Marijuana Authority (OMMA):

http://omma.ok.gov

• The Health Effects of Cannabis and Cannabinoids

https://www.nap.edu/catalog/24625/the-health-effects-of-

cannabis-and-cannabinoids-the-current-state

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Resources Cont.

• National Center for Complimentary and Integrative Health

https://nccih.nih.gov/health/marijuana

• American Cannabis Nurses Association –

http://americancannabisnursesassociation.org

• Society of Cannabis Clinicians - http://cannabisclinicians.org/

• American Academy of Cannabinoid Medicine -

http://aacmsite.org/

References

• American Nurses Association (ANA). 2016. Position Statement, Therapeutic Use of Marijuana and Related Cannabinoids, ANA Center of Ethics and Human Rights. Retrieved at http://www.nursingworld.org/positionstatements

• Baileys, K. 2018, APRNs must stay educated about medical cannabis in cancer care, ONS Voice.

• Bridgeman, M. & Abazia, D. Medicinal Cannabis: History, pharmacology, and implications for the acute care setting. P&T 2017; 42(3), pp.180-188.

• Cerda, M., Wall, M., & Feng, T. 2017. Association of state recreational marijuana laws with adolescent marijuana use, JAMA Pediatric, 171(2): 142-149.

• Drug Enforcement Administration, Diversion Control Division, Controlled Substances Act, Title 21 United States Code (USC), 2016. Food and Drugs, Chapter 13 Drug Abuse Prevention and Control. U.S. Government Printing office.

• Galli, J., Sawaya, R., & Friedenberg, F. (2011). Cannabinoid Hyperemesis syndrome, Current Drug Abuse Reviews, 4(4), 241-249.

• Merle, Renae, 2019. Banks want a hit of the marijuana business. Tulsa World 2/17/19. pp E1,E4, The Washington Post.

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References Cont.

• Morgan, C., Freeman, T., Powell, J., & Curran (2016). AK1 genotype moderates the acute psychotomimetic

effects of naturalistically smoked cannabis in young cannabis smokers. Translational Psychiatry, 6, e738.

• Morin, JF, Afzali, M., Bourque, J., Seguin, J. et.al (2018). a population-based analysis of the relationship

between substance use and adolescent cognitive development. The American Journal of Psychiatry.

Retrieved at https://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.2018.18020202

• NIH National Institute on Drug Abuse. (2018).Drug Facts. Marijuana as medicine. www.drugabuse.gov

• Oklahoma Medical Marijuana Authority (OMMA): http://omma.ok.gov

• Pettinato, M. (2017). Medicinal cannabis: a primer for nurses. Nursing, 47(8), pp.40-46.

• Pirschel,C. (2018). Understanding Medicinal Cannabis is Cancer Care. ONS Voice, January, 18-23.

• Schulmeister, L. 2018, The New MM: Medical Marijuana, Oncology Nursing News

• Small, E. and D. Marcus. 2002. Hemp: A new crop with new uses for North America. p. 284–326. In: J.

Janick and A. Whipkey (eds.), Trends in new crops and new uses. ASHS Press, Alexandria, VA.

https://www.hort.purdue.edu/newcrop/ncnu02/v5-284.html

References Cont.

• National Academies of Sciences, Engineering, and Medicine. 2017. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington, DC: The National Academies Press. https://doi.org/10.17226/24625.

• U.S. Food & Drug Administration, 2015. FDA and Marijuana: Questions and Answers. Retrieved at https://www.fda.gov/NewsEvents/PublicHealthFocus/ucm421168.htm

• U.S. Food & Drug Administration, 2015. How Drugs are Developed and Approved, Development & Approval Process. Retrieved at https://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/default.htm

• UpToDate. Retrieved at https://www.uptodate.com/contents/nabilone-drug-information?search=cesamet&source=panel_search_result&selectedTitle=1~18&usage_type=panel&kp_tab=drug_general&display_rank=1#F198735

• Whiting, P. et al. Cannabinoids for Medical Use: A systematic review and meta-analysis. JAMA. 2015:313(24): 2456-2473.

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