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:

• Terminology
• Legal Status
• Medical and Legal Considerations
• Pharmacology
• Drug Interactions
• Health Effects: Summary of the Evidence
• Asking Patients About Cannabis Use
• Educating Patients Regarding Responsible Use and Risks
• Conclusions
• Resources

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

• Screening and Referral for Cannabis Misuse and Cannabis Use Disorders
• Cannabis Toxicity
• Pregnant and Breastfeeding Women and Cannabis
• Youth and Cannabis

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 Health^12,13,14 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.

*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.”)

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:

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

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

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

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

• Medical Board of California Guidelines for the Recommendation of Cannabis for Medical Purposes  www.mbc.ca.gov/Publications/guidelines_cannabis_recommendation.pdf


• UCLA Cannabis Research Initiative
  www.uclahealth.org/cannabis
  Common cannabis-related terminology, general information about cannabis and its compounds, and information about current cannabis research.


• National Institute on Drug Abuse (NIDA) Marijuana
  https://d14rmgtrwzf5a.cloudfront.net/sites/default/files/1380-marijuana.pdf
  Information about NIDA’s role in providing cannabis for research, general information about cannabis and its compounds, summary of research, and statistics.

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

• Let’s Talk Cannabis
  http://publichealth.lacounty.gov/media/Cannabis
  Variety of resources including consumer, patient, and youth fact sheets.


• Los Angeles County DPH Substance Abuse Prevention and Control Program
  http://publichealth.lacounty.gov/sapc
  Information on prevention and the County’s specialty substance use disorder treatment system and services.


• CDC Health Effects of Marijuana
  www.cdc.gov/marijuana/index.htm
  Patient resources, FAQs and statistics.


• Los Angeles County DPH Medical Marijuana Program
  http://publichealth.lacounty.gov/eh/SSE/MedicalMarijuana
  Information about documentation needed to obtain a voluntary medical marijuana identification card, fees, office locations, and appointment information.

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.

References

1. California Health and Safety Code § 11362.77 (a-e). https://leginfo.legislature.ca.gov/faces/codes_displaySection.xhtml?sectionNum=11362.77&lawCode=HSC
2. Cannabis: Medicinal and Adult Use: Senate Bill No. 94: Sess. of 2017-2018 (2017). https://leginfo.legislature.ca.gov/faces/billTextClient.xhtml?bill_id=201720180SB94
3. State Marijuana Laws in 2018 Map. Governing. http://www.governing.com/gov-data/state-marijuana-laws-map-medical-recreational.html. Accessed May 11, 2018.
4. Title 21 Code of Federal Regulations. Part 1308: Schedules of Controlled Substances. §1308.11 Schedule I.(d)(31). https://www.gpo.gov/fdsys/pkg/CFR-2018-title21-vol9/pdf/CFR-2018-title21-vol9-chapII.pdf. Accessed May 18, 2018.
5. Drug Scheduling: Drug Schedules. United States Drug Enforcement Administration. https://www.dea.gov/drug-scheduling. Accessed August 31, 2018.
6. CA Business and Professions Code § 2525 – 2525.5. https://leginfo.legislature.ca.gov/faces/codes_displayText.xhtml?lawCode=BPC&division=2.&title=&part=&chapter=5.&article=25. Accessed August 31, 2018.
7. Brown, E, GnanaDev, D, Kirchmeyer, K. Medical Board of California: Guidelines for the Recommendation of Cannabis for Medical Purposes. http://www.mbc.ca.gov/Publications/guidelines_cannabis_recommendation.pdf. Accessed May 19, 2018.
8. Conant v. McCaffrey. United States District Court, 2000 WL 1281174 (N.D. Cal. Sept. 7, 2000).
9. Let’s Talk Cannabis FAQs. State of California, California Cannabis Portal. https://cannabis.ca.gov/faqs/. Accessed 31 August 2018.
10. Medical Marijuana Identification Card Program. MMP Frequently Asked Questions. Can a minor apply for a MMIC? California Department of Public Health. https://www.cdph.ca.gov/Programs/CHSI/Pages/MMICP-FAQs.aspx. Accessed August 31, 2018.
11. Let’s Talk Cannabis: Medicinal Use Cannabis Fact Sheet. California Department of Public Health, California Cannabis Health Information Initiative. https://www.cdph.ca.gov/Programs/DO/letstalkcannabis/CDPH%20Document%20Library/October%202017%20Update/CDPH-Medicinal.pdf. Updated October 17, 2017. Accessed July 10, 2018.
12. Medical Marijuana Identification Card Program. Roles and Responsibilities, County Responsibilities. California Department of Public Health. https://www.cdph.ca.gov/Programs/CHSI/Pages/MMICP-Roles-and-Responsibilities.aspx. Updated January 16, 2018. Accessed August 31, 2018.
13. Medical Marijuana Identification Card Program. MMP Frequently Asked Questions, Where Can I Apply for a MMIC? https://www.cdph.ca.gov/Programs/CHSI/Pages/MMICP-FAQs.aspx. Updated January 9, 2018. Accessed August 31, 2018.
14. California Health and Safety Code. § 11362.71. https://leginfo.legislature.ca.gov/faces/codes_displaySection.xhtml?lawCode=HSC&sectionNum=11362.71. Accessed August 31, 2018.
15. Medical Marijuana Identification Card Program. MMP Frequently Asked Questions, How Long is a MMIC Valid? California Department of Public Health. https://www.cdph.ca.gov/Programs/CHSI/Pages/MMICP-FAQs.aspx. Updated January 9, 2018. Accessed August 31 2018.
16. Medical Marijuana Program. Medical Marijuana Program Information. Los Angeles County Department of Public Health. http://publichealth.lacounty.gov/eh/SSE/MedicalMarijuana/. Accessed August 31, 2018.
17. California Revenue and Taxation Code § 34011 (f). https://leginfo.legislature.ca.gov/faces/codes_displaySection.xhtml?lawCode=RTC&sectionNum=34011. Accessed August 31, 2018.
18. Brady, K. Nightingale Z, Adams M. Practice Advisory: Immigration Risks of Legalized Marijuana. Immigrant Legal Resource Center. January 2018.  https://www.ilrc.org/sites/default/files/resources/marijuana_advisory_jan_2018_final.pdf. Accessed August 31, 2018.
19. FDA approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy. [news release]. Silver Spring, MD: U.S. Food and Drug Administration; June 25, 2018. https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm611046.htm.  Accessed July 12, 2018.
20. Ramesh, D. The Role and Clinical Implications of the Endocannabinoid System in Pain Processing. Topics in Pain Management. 2017;33(2):1-12.
21. Atakan Z. Cannabis, a complex plant: different compounds and different effects on individuals. Ther Adv Psychopharmacol. 2012;2(6):241-254. doi:10.1177/2045125312457586
22. Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol. 153(2):199–215. doi:10.1038/sj.bjp.0707442
23. Mechoulam R, Peters M, Murillo-Rodriguez E, Hanus LO. Cannabidiol - recent advances. Chemistry & Biodiversity. 2007;4(8):1678–1692. doi:10.1002/cbdv.200790147
24. Shannon S, Opila-Lehman J. Cannabidiol Oil for Decreasing Addictive Use of Marijuana: A Case Report. Integr Med (Encinitas). 2015;14(6):31-35.
25. Iffland K, Grotenhermen F. An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies. Cannabis Cannabinoid Res. 2017;2(1):139-154. doi:10.1089/can.2016.0034
26. Flockhart, DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine. 2007. https://drug-interactions.medicine.iu.edu/main-table.aspx. Accessed July 2, 2018.
27. Watanabe K, Yamaori S, Funahashi T, Kimura T, Yamamoto I. Cytochrome P450 enzymes involved in the metabolism of tetrahydrocannainols and cannabinol by human hepatic microsomes. Life Sci. 2007;(15):1415-1419.
28. Hartman RL. Brown TL, Milavetz, et al. Controlled Cannabis Vaporizer Administration: Blood and Plasma Cannabinoids with and without Alcohol. Clin Chem. 2015;61(6):850-869. doi:10.1373/clinchem.2015.238287
29. National Academies of Sciences, Engineering, and Medicine. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington, DC: The National Academies Press; 2017. doi:10.17226/24625
30. National Academies of Sciences, Engineering, and Medicine. The Health Effects of Cannabis and Cannabinoids, Committee’s Conclusions. http://nationalacademies.org/hmd/~/media/Files/Report%20Files/2017/Cannabis-Health-Effects/Cannabis-conclusions.pdf. Published January 2017. Accessed May 2, 2018.
31. Cooper ZD, Bedi G, Ramesh D, Balter R, Comer SD, Haney M. Impact of co-administration of oxycodone and smoked cannabis on analgesia and abuse liability. Neuropsychopharmacology . 2018;43(10):2046-2055. doi:10.1038/s41386-018-0011-2
32. Dryburgh LM, Bolan NS, Grof CPL, et al. Cannabis contaminants: sources, distribution, human toxicity and pharmacologic effects. Br J Clin Pharmacol. 2018. doi:10.1111/bcp.13695
33. Phase-in of Required Laboratory Testing. California Department of Consumer Affairs, Bureau of Cannabis Control. https://bcc.ca.gov/about_us/documents/17-261_required_testing_chart.pdf. Accessed August 31, 2018.
34. Proposed CA Business and Professions Code, § 5715.   https://www.bcc.ca.gov/law_regs/bcc_prop_text_reg.pdf. Accessed August 25, 2018.
35. National Academies of Sciences, Engineering, and Medicine. The Health Effects of Cannabis and Cannabinoids, Chapter Highlights. http://nationalacademies.org/hmd/~/media/Files/Report%20Files/2017/Cannabis-Health-Effects/Cannabis-chapter-highlights.pdf. Published January 2017. Accessed May 17, 2018.
36. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Arlington, VA: American Psychiatric Association; 2013.
37. Gorelick DA, Levin KH, Copersino ML, et al. Diagnostic criteria for cannabis withdrawal syndrome. Drug Alcohol Dep. 2012;123(1-3):141-147. doi:10.1016/j.drugalcdep.2011.11.007
38. Wallace EA, Andrews SE, Garmany CL, et al. Cannabinoid hyperemesis syndrome: literature review and proposed diagnosis and treatment algorithm. South Med J. 2011;104(9):659-664.
39. Kim HS, Monte AA. Colorado cannabis legalization and its effect on emergency care. Ann Emerg Med. 2016;68(1):71-75. doi:10.1016/j.annemergmed.2016.01.004
40. Synthetic marijuana: a dangerous drug at a cheap price. Centers for Disease Control and Prevention https://www.cdc.gov/nceh/hsb/synthetic_marijuana.htm. Updated December 12, 2013. Accessed August 14, 2017.
41. Thant T, Kondrad E, Nussbaum AM. Medical Marijuana: Indications, Formulations, Efficacy, and Adverse Events. In: Compton MT, ed. Marijuana and Mental Health. Arlington, VA: Publishing, American Psychiatric Association; 2016:71-94.
42. Synthetic Cannabinoids (K2/Spice). National Institute on Drug Abuse; National Institutes of Health; U.S. Department of Health and Human Services. https://www.drugabuse.gov/publications/drugfacts/synthetic-cannabinoids-k2spice. Accessed May 24, 2018.
43. Hartman, RL, Huestis MA. Cannabis effects on driving skills. Clin Chem. 2013;59(3):478-492. doi:10.1373/clinchem.2012.194381
44. Rogeberg, O, and Elvik R. The effects of cannabis intoxication on motor vehicle collision revisited and revised. Addiction. 2017;111(8):1348-1359. doi:10.1111/add.13347
45. Ramaekers JG, Robbe HW, O’Hanlon JF. Marijuana, alcohol and actual driving performance. Hum Psychopharmacol. 2000;15(7):551–558.