The Evolving Science and Policy of Cannabis: What Health Professionals Need to Know
[Up to 4 credits free CME available]

 

Eloisa Gonzalez, MD, MPH

Gary Tsai, MD, FAPA, FASAM

Jeff Chen, MD, MBA

Sarah Guerry, MD

September-October 2018

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As a result of shifting attitudes and policies, the marketplace for cannabis is rapidly evolving in Los Angeles County, including widespread advertising and availability of cannabis products. In contrast, there remains a lack of information on the health implications of cannabis use, in large part, due to federal research restrictions. As cannabis use increases in the county (see “LA Health: Recent Trends in Adult Use of Marijuana”), it is important that health care providers screen for cannabis use and prepare to have informed discussions with their patients. This article is designed to educate health care providers on the most clinically relevant cannabis issues and covers the following topics:

Providers are encouraged to read the following supplemental articles for more in-depth information:

Terminology

Cannabis is the scientific name for marijuana. Cannabis contains a variety of active compounds, including cannabinoids. For the purposes of this article, cannabis refers to the plant and the products derived from the plant, whereas cannabinoid refers to the specific group of active compounds.

In this article, medicinal cannabis will be used to refer to cannabis use that is either recommended by a physician or initiated by a patient to treat a medical condition. The term non-medicinal cannabis will be used to refer to the use of cannabis for the purpose of seeking a pleasurable effect or “high.” Non-medicinal use is preferred over the term recreational use because recreation is associated with healthy practices, such as physical activity.

See the UCLA Cannabis Research Initiative terminology webpage for a glossary of terms associated with cannabis.

 

Legal Status

California became the first state in the United States to legalize medicinal cannabis with the Compassionate Use Act in 1996.1 More recently in 2016, California voters approved the Control, Regulate and Tax Adult Use of Marijuana Act (AUMA), which legalized the non-medicinal use of cannabis by anyone 21 years of age and older.2 As of January 2018, 29 states and the District of Columbia have legalized cannabis for either medicinal or non-medicinal adult use.3

Despite the growing trend of cannabis legalization, cannabis and one of its main active compounds, Δ9-tetrahydrocannabinol (THC), remain federally classified as Schedule I drugs under the U.S. Controlled Substances Act.4 Schedule I drugs, which include heroin and LSD, are defined as having a high potential for abuse and no currently accepted medical use.5 There are significant federal research restrictions on Schedule I drugs.

 

Medical and Legal Considerations

There are several medical and legal considerations health care providers should be aware of regarding cannabis.

  • California physicians cannot dispense or prescribe Schedule I drugs such as cannabis, but they can recommend cannabis to patients.6 Note: FDA-approved cannabinoids are not Schedule I drugs and can be prescribed. (See “FDA-Approved Cannabinoids.”)

  • Physicians should be familiar with and follow the Medical Board of California (MBC) Guidelines for the Recommendation of Cannabis for Medical Purposes if recommending cannabis to patients. In these revised guidelines from April 2018, the MBC states that it will not take disciplinary action for recommendations made “in accordance with the accepted standards of medical responsibility."7 Moreover, since 2000, federal case law has ruled that federal agencies cannot take action against a physician solely because he/she recommended cannabis in the routine course of medical care.8 

  • Anyone age 21 years of age or older can legally purchase cannabis in California without a physician’s recommendation.2 However, there are reasons that patients may want a physician’s recommendation for cannabis, such as to seek medical guidance or to obtain a Medical Marijuana Identification Card.

  • Patients aged 18 years and older,9 as well as emancipated minors, can legally purchase and use cannabis in California for medicinal use with a physician’s recommendation.

  • Pediatric patients under 18 years of age can also legally use cannabis for medicinal purposes if they have a physician’s recommendation. In order to purchase the pediatric patient’s medicinal cannabis, the child’s adult primary caregiver must have a Medical Marijuana Identification Card on the child’s behalf.10,11 Note: A minor who is a parent of a qualified patient can be designated the primary caregiver and obtain a Medical Marijuana Identification Card to purchase cannabis for that child.

  • In LA County, Medical Marijuana Identification Cards are issued exclusively by the LA County Department of Public Health12,13,14 and are valid up to one year.15 A physician recommendation is required to obtain a card.16 These cards provide exemption from certain sales taxes17 and are required to obtain medicinal use cannabis for minors. In addition, the cards authorize the use, possession, and transport of medicinal cannabis in California.11 See the California Cannabis Health Information Initiative’s “Medicinal Use Cannabis” fact sheet for more information.

  • As cannabis remains illegal at the federal level, cannabis use and/or possession, whether medicinal or non-medicinal, may incur federal consequences. In the case of immigration status, current or past cannabis use may impact immigration status.18 See the Immigrant Legal Resource Center’s "Immigrants and Cannabis” fact sheets, which are available in multiple languages.

 

FDA-Approved Cannabinoids

There are currently four FDA-approved cannabinoids available in the United States.

Generic (Brand) Formulation Schedule
Cannabidiol (CBD)/Epidiolex liquid purified CBD from cannabis V*
Dronabinol/Marinol oral capsule synthetic THC III
Dronabinol/Syndros liquid synthetic THC II
Nabilone/Cesamet oral capsule synthetic THC analogue II

 

*In June 2018, the FDA approved Epidiolex (purified CBD) for the treatment of seizures associated with two rare and severe forms of pediatric epilepsy, Lennox-Gastaut syndrome and Dravet syndrome, in patients two years of age and older.19 All CBD products other than Epidiolex remain Schedule I. Epidiolex is the first cannabis-derived product to be approved by the FDA. The other FDA-approved drugs are synthetic and not cannabis-derived.

Pharmacology

The cannabis plant contains unique compounds called cannabinoids, which exert physiologic effects, in part, by binding to cannabinoid receptors. These receptors are involved in a variety of processes including mood, memory, sleep, appetite, pain, metabolism, and immune function.20

At least 70 different cannabinoids have been identified in cannabis, with the most studied being Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD).21

  • THC is the most abundant cannabinoid found in cannabis and is associated with the psychoactive and euphoric effects of cannabis.22,23
  • CBD is the second most abundant cannabinoid found in cannabis. Unlike THC, CBD is non-psychoactive, has no abuse potential, and may even possess anti-addictive properties.24,25

 

Drug Interactions

Data are limited regarding drug interactions associated with cannabis use. However, there are potential drug interactions based on the known metabolism of the primary cannabinoids in cannabis.

THC and CBD interact with CYP liver enzymes and can increase or decrease the concentrations of other drugs (Figure 1).26,27 Alcohol may also increase THC levels.28 Patients should be advised that cannabis may have adverse interactions with prescription medications and alcohol, and patients known to use cannabis should be monitored for potential drug interactions. (See “Drug Interactions.”)

 

THC and CBD Impact on Medication Concentrations

 

Health Effects: Summary of Evidence

In 2017, The National Academies of Sciences, Engineering, and Medicine (NASEM) published a landmark review titled “The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research” that summarized available scientific research regarding the potential therapeutic effects and health risks of cannabis and cannabinoids.29 NASEM presented nearly 100 conclusions that are summarized in the review.30 The major findings are summarized below.

 

Therapeutic Effects

To determine potential therapeutic effects of cannabis, NASEM reviewed clinical trials designed to investigate the effects of cannabis or cannabinoids on specific conditions. As previously mentioned, the federal classification of cannabis as a Schedule I drug severely limits research activities and types of study material (cannabis products) eligible for therapeutic cannabis research in the U.S. There have been no controlled clinical studies of specific cannabis products available in U.S. dispensaries today, such as cannabis flower, edibles, beverages, topicals, and concentrates.29 In addition, no controlled clinical studies of cannabis/cannabinoids in any pediatric populations were found during the NASEM review. Of note, clinical trials of CBD to treat certain forms of pediatric epilepsy were published after the January 1, 2017 NASEM review cutoff date. (See “FDA-Approved Cannabinoids.”)

NASEM concluded that cannabis or cannabinoids are modestly effective for adults with the following conditions when administered via specific routes:

  • Chronic pain (cannabis* or oral cannabinoids**)
  • Chemotherapy-induced nausea and vomiting (oral cannabinoids**)
  • Multiple sclerosis (MS)-related spasticity (oral cannabinoids**)

* Cannabis refers to smoked/vaporized cannabis, which contains many active cannabinoid compounds.
** Oral cannabinoids refer to pharmaceutical preparations of individual cannabinoids. This does not include edibles or other oral forms of cannabis available in dispensaries.

 

NASEM also concluded there was inadequate information to assess the therapeutic effects of cannabis or cannabinoids for all the other conditions that were evaluated:

  • Addiction
  • Amyotrophic lateral sclerosis
  • Anorexia and weight loss associated with HIV
  • Anxiety
  • Cancer
  • Dementia
  • Depression
  • Dystonia
  • Epilepsy
  • Glaucoma
  • Huntington’s disease
  • Irritable bowel syndrome
  • Parkinson’s disease
  • Post-traumatic stress disorder
  • Schizophrenia and other psychoses
  • Sleep disorders
  • Spasticity
  • Tourette syndrome
  • Traumatic brain injury

 

Chronic Pain

Though clinical trials have shown that cannabis is effective at reducing pain symptoms in adults, the efficacy and safety of current forms of cannabis and cannabinoids available in U.S. dispensaries remains unclear. Given that pain is the most commonly cited reason for medicinal cannabis use by patients,29 it is likely that more adults will self-treat their chronic pain with cannabis. However, whether cannabis should be considered as a non-opioid therapy for chronic pain remains unclear despite recent reports suggesting that cannabis administration may reduce the use of opioid-based pain medications.31 Clinicians caring for patients with chronic pain should ask them directly about cannabis use (see “Asking Patients About Cannabis Use”), provide appropriate education, and monitor for misuse and drug interactions.

 

Therapeutic Effects Summary

The NASEM findings of effectiveness for cannabis and/or cannabinoids in the treatment of adults with chronic pain, chemotherapy-induced nausea and vomiting, and MS-related spasticity are promising for the medical care of these conditions. Although there is a lack of evidence supporting the use of cannabis or cannabinoids for other conditions that were evaluated, some are listed by the MBC as debilitating conditions that qualify the patient for a medical marijuana recommendation (e.g., cancer, anorexia, AIDS, glaucoma, and migraine). MBC states that due to the lack of evidence of efficacy in the treatment of certain conditions, physicians should use their professional discretion and base medicinal cannabis recommendations on informed and shared decision making with their patients. (See MBC’s “Guidelines for the Recommendation of Cannabis for Medical Purposes.”)

 

Other Health Effects

To ascertain the impacts of non-medicinal cannabis use on health, NASEM reviewed epidemiologic studies investigating the associations and risk factors of smoked cannabis and various health conditions. The table below features the key highlights regarding these health effects. Bolded findings had the most significant evidence base for harm.

There are important limitations to these findings. The conclusions are based on epidemiologic studies that show associations but cannot confirm causality. Moreover, these studies generally examined non-medicinal use, which may entail different patterns of use and different levels of THC and CBD compared with medicinal cannabis use. In addition, the findings may not be generalizable to cannabis available for legal purchase today. As smoked cannabis was the only delivery route examined in these studies, these effects may not apply to other forms of cannabis consumption. In addition, it is unknown if and to what degree contaminants contributed to the observed effects. Contaminants in cannabis are prevalent and have poorly understood health effects.32 To address this, for the first time since California legalized medical cannabis in 1996, standards are being implemented for the testing of bacteria, chemicals, pesticides, fertilizers, and heavy metals in cannabis products.33 In California, since January 1, 2018, only those cannabis products that pass testing may be legally sold.34

 

Table 1: Health Effects of Cannabis Use35

Prenatal,
Perinatal, and Neonatal Exposure

  • Smoking cannabis during pregnancy is linked to lower birth weight in the offspring.
  • The relationship between smoking cannabis during pregnancy and other pregnancy and childhood outcomes is unclear.

Injury and Death

  • Cannabis use prior to driving increases the risk of being involved in a motor vehicle accident.
  • In states where cannabis use is legal, there is increased risk of unintentional cannabis overdose injuries among children.
  • It is unclear whether and how cannabis use is associated with all-cause mortality or with occupational injury.

Psychosocial

  • Recent cannabis use impairs performance in the cognitive domains of learning, memory, and attention. Recent use may be defined as cannabis use within 24 hours of evaluation.
  • Cannabis use during adolescence is related to impairments in subsequent academic achievement and education, employment and income, and social relationships and social roles.
  • A limited number of studies suggest that that impairment persists  in the cognitive domains of learning, memory, and attention in individuals who have stopped smoking cannabis.

Mental Health

  • Cannabis use is likely to increase the risk of developing schizophrenia and other psychoses in predisposed individuals – the greater the use, the higher the risk.
  • For individuals diagnosed with bipolar disorders, near daily cannabis use may be linked to greater symptoms of bipolar disorder than among non-users.
  • Heavy cannabis users are more likely to report thoughts of suicide than non-users.
  • Regular cannabis use is likely to increase the risk of developing social anxiety disorder.
  • In individuals with schizophrenia and other psychoses, a history of cannabis use may be linked to better performance on learning and memory tasks.
  • Cannabis use does not appear to increase the likelihood of developing depression, anxiety, and post-traumatic stress disorder.

Problem
Cannabis Use

  • Greater frequency of cannabis use increases the likelihood of developing problem cannabis use.
  • Initiating cannabis use at a younger age increases the likelihood of developing problem cannabis use.

Cannabis Use
and Abuse of
Other Substances

  • Cannabis use is likely to increase the risk of developing other substance use disorders (other than cannabis use disorder).

Respiratory Disease

  • Smoking cannabis on a regular basis is associated with chronic cough and phlegm production.
  • Quitting cannabis smoking is likely to reduce chronic cough and phlegm production.
  • It is unclear whether cannabis use is associated with COPD, asthma, or worsened lung function.

Cardiometabolic Risk

  • The evidence is unclear as to whether and how cannabis use is associated with heart attack, stroke, and diabetes.

Cancer

  • The evidence suggests that smoking cannabis does not increase the risk for certain cancers (i.e., lung, head, and neck) in adults.
  • There is modest evidence that cannabis use is associated with one subtype of testicular cancer.
  • There is minimal evidence that parental cannabis use during pregnancy is associated with greater cancer risk in offspring.

Immunity

  • There is a lack of data on the effects of cannabis or cannabinoid-based therapeutics on the human immune system.
  • There is insufficient data to draw overarching conclusions concerning the effects of cannabis smoke or cannabinoids on immune competence.
  • There is limited evidence to suggest that regular exposure to cannabis smoke may have anti-inflammatory activity.
  • There is insufficient evidence to support or refute a statistical association between cannabis or cannabinoid use and adverse effects on immune status in individuals with HIV.
 

Source: Adapted from NASEM “The Health Effects Of Cannabis and Cannabinoids Chapter Highlights.”

 

Summary of Other Health Effects

NASEM found significant evidence of adverse effects associated with non-medicinal cannabis use across many health categories. In particular, cannabis users are at a higher risk of motor vehicle crashes and substance use disorders. In pregnancy, cannabis use is linked to low birth weight in infants. In addition, cannabis use during adolescence is associated with substantial risks including addiction and adverse impacts on academic achievement, employment, and social functioning.

 

Other Adverse Health Findings

There are other adverse health findings related to cannabis that were not described in the NASEM report, including cannabis use disorder,36 cannabis withdrawal syndrome,37 and a newly described cannabinoid hyperemesis syndrome.38,39 (See supplemental article on “Cannabis Toxicity” for details.)

 

Asking Patients About Cannabis Use

General Screening

It is important for healthcare providers to ask their patients about cannabis use in a non-judgmental manner, and to provide unbiased and evidence-based information. A question such as, “Are you using any cannabis or cannabis products such as marijuana, hemp, THC, or CBD?” may be included in a patient intake form and/or asked in-person. Affirmative answers should be followed up with questions about how they consume the products and the frequency of use. Due to the association between addiction and cannabis, providers are encouraged to ask cannabis users if they think their cannabis use is causing problems. If the patient responds affirmatively and is amenable to treatment, a referral for substance use disorder treatment is generally warranted. See supplemental article, “Screening for Cannabis Misuse and Substance Use Disorders,” for screening tools and treatment referral information.

Understanding Current Cannabis Products and Method of Consumption

Medical providers should be aware that patients may be consuming cannabis via various routes, such as smoking, vaporizing, eating, drinking, and dermal application (Figure 2).40,41,42

 

Origin and Consumption Methodsof Natural and Synthetic Cannabinoid Products

 

Key Points:

  • Cannabis products can be legally obtained from licensed dispensaries. Patients should be advised that higher levels of THC are found in some of the newer cannabis products such as dabs, vape oil, and/or edibles.

  • In addition to cannabis plants, hemp plants are a source of naturally occurring CBD. CBD derived from hemp is sold widely throughout the U.S. and consumers may not associate it with cannabis. Hemp-derived CBD products sold outside of dispensaries are not regulated like cannabis-derived CBD products sold in dispensaries and thus may not contain the levels of CBD advertised or may contain contaminants. Patients known to use CBD/hemp should be monitored for potential drug interactions.

  • It is important to assess the patient’s utilization of synthetic cannabinoids (also known as synthetic marijuana, Spice, K2, and other names). Despite the name, these synthetic psychoactive drugs are not cannabis, are not sold in licensed cannabis dispensaries, and tend to have unpredictable and significantly more dangerous and life-threatening effects than cannabis.42 Synthetic cannabinoids may be sold as liquids for vaping or sprayed on dried plant material to be smoked and are often marketed as herbal or liquid incense. All non-prescription synthetic cannabinoids are illegal in the U.S. See the CDC webpage “Synthetic cannabinoids: What are they? What are their effects?” to learn more about synthetic cannabinoids.

 

Educating Patients Regarding Responsible Use and Risks

It is important that healthcare providers are prepared to discuss the risks of cannabis use and how adults can use cannabis responsibly, if they choose to use it. Below are key counseling points with links to more detailed information and resources.

 

Table 2: Cannabis Counseling Points and Resources

COUNSELING POINT: Cannabis use is discouraged among women who are pregnant, breastfeeding, or contemplating pregnancy.

Provider Information Patient Information

COUNSELING POINT: Protect infants and children from cannabis exposure including secondhand smoke and unintentional poisoning from edibles and other products such as patches and tinctures. 

Advise patients to store all cannabis products in a locked area, out of a child’s view and reach, and in the original child-resistant packaging from the dispensary.

Provider Information Patient Information

COUNSELING POINT: It is illegal for anyone under 21 years of age to smoke, consume, buy, or possess non-medicinal cannabis. Cannabis has several negative effects in youth.

Provider Information Patient Information  

COUNSELING POINT: Do not drive when under the influence of cannabis.

Driving while under the influence (DUI) of cannabis is unsafe and illegal. Cannabis use prior to driving increases the risk of being involved in a motor vehicle crash.43,44 Studies show that cannabis impairs psychomotor skills, lane tracking, and cognitive functions.43,45 Impaired drivers may be arrested and convicted for DUI, regardless of the substance causing the impairment (e.g., cannabis, alcohol, prescription medications, street drugs).

Provider Information Patient Information

COUNSELING POINT: Be aware of high levels of THC.

Many cannabis plants now have higher amounts of THC and newer methods of consuming cannabis (e.g., dabbing, vaping, and/or consuming edibles) tend to deliver higher doses of THC into the body, which increases risk of impairment, acute psychosis, and poisoning.

Provider Information Patient Information

COUNSELING POINT: Be aware of synthetic cannabinoids (e.g., K2, Spice, Kush).

Synthetic cannabinoids are not cannabis and are often more dangerous. 

Provider Information Patient Information

COUNSELING POINT: Be aware of contaminants in cannabis products.

Advise patients to only purchase cannabis products from licensed dispensaries.

Provider Information Patient Information

COUNSELING POINT: Be aware that there are legal limits for medicinal and non-medicinal cannabis use, and that penalties are associated with exceeding limits. Limits are higher for medicinal use.

Provider Information Patient Information
  • Fact Sheet: Medicinal Cannabis Use Limits  English    Spanish
  • Fact Sheet: Medicinal Cannabis Use Penalties English    Spanish
  • Fact Sheet: Non-medicinal Adult Cannabis Use Limits English   Spanish
  • Fact Sheet: Non-medicinal Adult Cannabis Use Penalties English   Spanish

COUNSELING POINT: Be aware that cannabis may impact immigration status.

Cannabis is still illegal at the federal level and may have repercussions on immigration status for patients.

Provider Information Patient Information
 

Conclusions

The wide availability of cannabis is a significant public health concern, particularly for vulnerable populations such as adolescents and pregnant women. Though evidence is limited for the impact of cannabis on most conditions, research in adults suggests clinical benefit for three conditions: chronic pain, chemotherapy-induced nausea and vomiting, and spasticity due to multiple sclerosis.

The MBC has issued guidelines for the recommendation of cannabis for medicinal purposes, while allowing physicians to use their clinical judgment to decide on the appropriateness of medicinal cannabis for their patients. However, cannabis has been associated with an array of harmful health effects and may cause certain drug interactions. Therefore, medical providers should routinely ask patients about their use of cannabis and be prepared to have informed conversations with patients about the possible health effects of cannabis and illegal synthetic cannabinoids. Finally, providers should stay abreast of the ever-growing body of research on cannabis, as the evidence of the health impacts of cannabis use is sure to evolve and expand.

 

Resources

Guidelines and Research

 

Drug Interactions

  • WebMD-Marijuana
    www.webmd.com/vitamins/ai/ingredientmono-947/marijuana
    Information on uses, side effects, interactions, and dosing of cannabis/cannabinoids.

  • Medical Cannabis: Adverse Effects and Drug Interactions
    https://dchealth.dc.gov/dcrx
    A one-credit CME course offered by the District of Columbia Department of Health that provides evidence-based information on the safety profile of medicinal cannabis. Includes common contraindications, adverse effects, and drug interactions. Download the slides or visit the website to access the course.

 

Poison Control

  • California Poison Control System’s 24-hour Hotline
    800-222-1222
    https://calpoison.org
    Helpline for patients, families and all health care providers. Experts in poisoning information tailor advice based on the patient’s medical history and specific exposure. Advise patients to program the Hotline phone number into their phones so that it is readily available in the event of unintentional ingestion and/or cannabis overdose. 

  • Los Angeles County DPH Poison Treatment Website
    http://publichealth.lacounty.gov/eh/TEA/ToxicEpi/poisontreatment.htm

 

Patient Resources

 

Policies and Regulations

  • Los Angeles County Office of Cannabis Management
    http://cannabis.lacounty.gov
    Information regarding the implementation of the County’s cannabis policies and regulations.

  Continuing Medical Education
 
 
 

Continuing Medical Education

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References

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Author Information:

Eloisa Gonzalez MD, MPH
Director, Cardiovascular and School Health*
Director, Integrative Medicine, The Wellness Center at LA County Historic General Hospital**

Gary Tsai, MD, FAPA, FASAM
Medical Director and Science Officer, Substance Abuse Prevention and Control*

Jeff Chen MD, MBA
Director, Cannabis Research Initiative***

Sarah Guerry, MD
Chief, Medical Education and Communication*

*County of Los Angeles
Department of Public Health

**County of Los Angeles
Department of Health Services

***University of California,
Los Angeles

Elgonzalez@ph.lacounty.gov


Acknowledgments:

The authors would like to thank the following people for their contributions:

Research support:
Kay Hooshmand, DO, MPH (UCLA); Jo (Mulun) Huang (UCLA); Gina Johnson, BS (UCLA); Dan Li, BA (UCLA); and Kelly Yeo, BS (UCLA).

Article review and feedback:
Rosemary Flores, MD (Permanente Medical Group); Jaime Gonzalez, MD (Vituity Emergency Medicine); Michelle Ann Higley, MD; Kay Hooshmand, DO, MPH, (UCLA); Nalini Nauth Otello, MD, FAAP (Permanente Medical Group); and Celina Barba-Simic, MD, (Burbank Emergency Medical Group and Providence Saint Joseph Medical Center).


Rx for Prevention, 2018
September-October;8(5).


Published: September 13, 2018
Updated: October 4, 2018