By Lixia Chen, Ph.D

December 4, 2018 Insights

Marijuana, also known as cannabis, is a plant material obtained from cannabis sativa. It is used as medication or recreational purposes. Although the Cannabis plant contains hundreds of compounds, delta-9-tetrahydrocannabinol (Δ9-THC or THC) is psychoactive and produces several pharmacological effects. Hashish is the product created from the resin of marijuana flowers.  Hash oil or cannabis oil is an oleoresin extracted from cannabis or hashish.

Prevalence of marijuana use

In 2016, the Centers for Disease Control and Prevention (CDC) published a review of federal statistics of marijuana use in the United States (U.S). One conclusion of the study was that marijuana use in the past year increased among persons aged ≥12 years from 11% in 2002 to 13.2% in 2014.1 In a more recent study, The National Institute on Drug Abuse (NIDA)/National Institute on Drug Abuse (NIH)/National Household Survey on Drug Abuse (NHSDA) indicated that marijuana use in the past year increased among persons aged ≥12 years from 13.9% in 2016 to 15% in 2017.2 A large survey (36,000 individuals surveyed) published in 2015 in Journal of the American Medical Association (JAMA) Psychiatry, also found that the prevalence of marijuana use in the U.S more than doubled over a ten year period. The percentage of adults (≥ 18 years) who reported using marijuana in the past year increased from 4.1 % in 2001–2002 to 9.5 % in 2012–2013.3

The data from these surveys indicate that marijuana use increased in both males and females in the adult group (≥18) from 2002 to 2017; however, among the younger age bracket (12–17) marijuana use had decreased from 2002 to 2014 with a recent increase in the last few years. CDC data suggest that the prevalence of past-year marijuana use decreased from 15.8% in 2002 to 13.1% in 2014 among persons aged 12–17 years, but more recently, NIDA/NIH/NHSDA indicated that past-year marijuana use increased among persons aged 12–17 years from 12% in 2016 to 12.4% in 2017.

Federal and state law for marijuana use

Increases in the availability of marijuana due to changes in state laws may contribute to this rise in marijuana use, but findings cannot be used to infer causality.2,3 As of November  2018, thirty three states and the District of Columbia currently have laws legalizing marijuana in some form. Also, ten states and the District of Columbia have adopted more expansive laws legalizing marijuana for recreational use.4 The different policies regarding legality of marijuana are expanded upon below.

Decriminalization: The term decriminalization refers to a policy in which individuals have no criminal prosecution from possessing small amounts of cannabis. It will be treated as to a lesser type of civil penalty, similar to a minor traffic violation. Since 1973, twenty-two states and the District of Columbia have decriminalized the possession of small amounts of marijuana.

Medical use of marijuana: Medical marijuana is a plant-based medicine from the Cannabis sativa or Cannabis species with three major active compounds: THC, Cannabidiol (CBD), and Cannabinol (CBN). Medical use of marijuana was approvedas early as 1996 in California. A total of 33 states and the District of Columbia now allow for comprehensive public medical marijuana use.

Recreational use: In 2012, Colorado first legalized recreational use of Marijuana. After that, ten states and the District of Columbia have adopted laws legalizing recreational use of marijuana.

In Massachusetts, marijuana was decriminalized in 2008. The new law means that an individual possessing up to one ounce of marijuana will not receive criminal penalties. Voters have approved the use of marijuana for the following indications: personal use, cultivation, and distribution. A prescription is required for medical use in 2012 and recreational use of marijuana became legal in Massachusetts in 2016. A Cannabis Control Commission was formed by the Commonwealth of Massachusetts to oversee the introduction of retail sales. As of September 2018, thirteen companies have been approved for Provisional Licenses as a Retailer, Cultivator, or Product Manufacturer, and two laboratories were approved for Provisional Licenses for Independent Testing. Retail shops applied for licenses to sell gel capsules, sublingual tinctures, balm, edibles, and pre-filled vaporizer cartridges.

State relaxation of the use of marijuana does not affect its federal status. It is currently classified as a Schedule I controlled substance according to the 1973 Controlled Substances Act. Schedule I drugs are referred as drugs with no currently accepted medical use but a high potential for abuse.

Marijuana use disorder

Physiological effects of marijuana include rapid changes in heart rate and diastolic blood pressure, conjunctival suffusion, dry mouth and throat, increased appetite, and decreased respiratory rate. Cannabis also affects the immune and endocrine systems, and abuse is associated with lung damage and EEG alterations..

Marijuana (or Cannabis) use disorder (CUD), also known as marijuana addiction, is defined as the continued use of cannabis despite having persistent clinically significant impairment.5 CUD is often associated with other substance use disorders, behavioral problems, and disability. Potential consequences of marijuana use include impaired functioning, vehicle accidents while under the influence of the effects of cannabis, emergency department visits, psychiatric symptoms, and addiction.

One study has demonstrated that the risk for marijuana use and CUD increased significantly in states that passed medical marijuana laws compare to in states that did not.3 Also, recent analysis by Zlatko Mehmedic et al stated that the marijuana content of cannabis plants suggests increased potency of the plant material in recent years with high levels of Δ9-THC and low levels of other phytocannabinoids such as cannabidiol (CBD). Between 1993–2008 data showed an upward trend in the mean Δ9-THC content of all confiscated cannabis preparations, increasing from 3.4% in 1993 to 8.8% in 2008.6  Higher THC levels may explain the increase of CUD.

Marijuana edibles are food products made with marijuana or marijuana oils. They can be used for smoking or vaporizing marijuana. Edibles come in many different food types including brownies, candies, cookies, gummies in animal or fruit-shape, chocolates, drinks, and popcorn. In marijuana edible products, the amount of THC can vary, which makes it more difficult to control the consumed amount of THC.

Δ9-THC is a highly lipophilic compound which is distributed in the adipose tissue, liver, lung, and spleen. Hydroxylation of Δ9-THC generates the psychoactive compound 11-hydroxy Δ9_Tetrahydrocannabinol (11-OH-THC) and further oxidation generates the inactive 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCCOOH). This is then conjugated with glucuronic acid to form THCCOOH glucuronide. The parent compound and/or the metabolites may be the target of laboratory testing.

Laboratory Testing

1) Presumptive Drug Testing

The most common screening methods used to detect marijuana/cannabinoid in urine is by enzyme immunoassay (EIA). THCCOOH is usually detected by EIA; however, due to cross-reactivity, other cannabinoids present in the urine may also be reactive with the marijuana/ cannabinoid EIA. Therefore, immunoassay results are expressed in terms of “total cannabinoids” and not specifically in terms of THCCOOH concentration. The cut off or threshold reporting limit  for detection of cannabinoids used by the US Substance Abuse and Mental Health Services Administration (SAMHSA) is 50 ng/mL.

2) Definitive Drug Testing

Gas chromatography–mass spectrometry (GC-MS) or Liquid Chromatography with tandem mass spectrometry (LC-MS-MS) can be used for identification confirmation as one use of definitive drug testing. The specimen type and advantages and/or disadvantages are shown in the table below (Table 1).

Table 1.Confirmation Testing of Marijuana from different specimen type.

Urine Blood Hair Saliva/oral fluid
Target analyte for testing

 

THCCOOH THC

11-OH-THC

THCCOOH

 

THC

11-OH-THC

THCCOOH

 

THC

 

Assay explanation

 

Urine tests detect the non-psychoactive marijuana metabolite – THCCOOH – but do not detect the psychoactive component THC in marijuana, and therefore do not measure impairment. Blood tests are a better indicator of recent use, since they measure the presence of activeTHC in the system. Blood tests are used less frequently due to being invasive and difficult to administer. Hair tests do not measure current use, but rather chronic exposure.

 

Saliva testing is performed to detect recent use, and depending on the drug mayrangefrom several hours to over a day.

 

 

The length of time cannabinoids may be detected in the human body depends upon many factors including the specimen to be tested, the target analyte, the sensitivity and specificity of the assay, and individual variables such as the frequency, dose, last time of use, genetic composition, and the function of the metabolic, digestive, and excretory systems. When interpreting THC concentrations, it is important to know which sample type has been tested and which target compound has been analyzed. While immunoassay cross-reactivity to non-cannabinoid compounds is rare, it is recommended that positive presumptive results are confirmed by mass spectrometry-based analytical methods such as GC-MS and LC/MS/MS which provide definitive test results.In summary, with legalization of marijuana for medical and recreation use and increasing potency of THC levels in marijuana products, more attention needs to be focused on marijuana usage and tests. Clinician can select different tests for the use of marijuana based on a variety of purposes and available sample type.

References:
1. https://www.cdc.gov/mmwr/volumes/65/ss/ss6511a1.htm?mbid=synd_yahoohealth
2. https://www.drugabuse.gov/national-survey-drug-use-health
3. Deborah S. Hasin, Aaron L. Sarvet, Magdalena Cerdá, et al. US Adult Illicit Cannabis Use, Cannabis Use Disorder, and Medical Marijuana Laws 1991-1992 to 2012-2013. JAMA Psychiatry. 2017;74(6):579-588. doi:10.1001/jamapsychiatry.2017.0724
4. http://www.governing.com/gov-data/safety-justice/state-marijuana-laws-map-medical-recreational.html
5. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing.
6. Mehmedic Z, Chandra S, Slade D, et al. Potency trends of Δ9-THC and other cannabinoids in confiscated cannabis preparations from 1993 to 2008. J Forensic Sci.2010;55(5):1209-1217. doi:10.1111/j.1556-4029.2010.01441.x.