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Cannabis Use

General Information

Description

  • cannabis use refers to the consumption of products from the cannabis plant, typically for recreational or spiritual reasons2,3,4
    • intoxicating effects of cannabis may include relaxation, disassociation, and euphoria, though psychological reactions vary on an individual basis
    • currently cannabis is the most commonly used illicit substance in United States and worldwide
    • adverse effects and complications from cannabis use may be increasing due to increasing availability, potency, and new methods of ingestion
  • cannabis use disorder refers to continued problematic use despite negative consequences that causes significant distress or impairment in functioning2,4
  • synthetic cannabinoid-like compounds are not within the scope of this topic
  • for medicinal uses of cannabis, see Medical uses of cannabinoids topic

Definitions

  • terms referring to cannabis plant or plant products3
    • hemp - tall, fibrous plant grown for rope or fabric; contains very low delta-9 tetrahydrocannabinol (THC) concentrations
    • cannabis
      • annual flowering herb (also called marijuana)
      • 2 main species are Cannabis sativa and Cannabis indica
  • cannabis use terms1,2,4
    • cannabis intoxication typically refers to the acute psychological effects of cannabis ingestion or cannabis smoke inhalation
    • cannabis use disorder refers to continued problematic use despite negative consequences that causes significant distress or impairment in functioning. and may be defined as meeting ≥ 2 Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria (found below in Making the diagnosis) within a 12-month period
    • cannabis withdrawal refers to a constellation of several negative effects of cannabis cessation experienced by individuals who have had daily or near daily use for ≥ few months (criteria found below in Making the diagnosis)
  • synthetic cannabinoid-like compounds (not covered in this topic) are also referred to as spice, K2, kush, potpourri, skunk, aroma, and moon rocks (27273001J Addict Nurs 2016 Apr-Jun;27(2):154)

Mechanism of action

  • effects of cannabis are caused by the ingested cannabinoids exerting action within endocannabinoid system
    • endocannabinoid system functions parallel to and in conjunction with adrenergic, cholinergic, and dopaminergic systems
    • endocannabinoid system includes 3 major components
      • endogenous receptors, CB1 and CB2 found in central and peripheral nervous system
        • CB1 receptors localized in central nervous system involved in
          • modulation of mood, motor tone and coordination, and cognition (such as concentration, short-term memory, attention, and tracking behavior)
          • abuse potential and dependence
        • CB1 receptors localized in peripheral nervous system modulate
          • energy metabolism by promoting fat deposition and insulin resistance
          • food intake, visceral sensation, gastrointestinal motility, gastric secretion, intestinal inflammation, and cell proliferation
        • CB2 receptors found in periphery (mainly on immune cells) function to regulate
          • cellular and humoral response to neuroinflammation and pain
          • gastrointestinal functions of digestion and host defense
        • endocannabinoids may act at other receptors such as the capsaicin receptor (TRPV1), G protein-coupled receptors 55 and 119, transient receptor potential of melastatin type 8 channel, 5-HT1a receptor, alpha-3 and alpha-1 glycine receptors, and transient receptor potential of ankyrin type 1 channel
      • endogenous cannabinoids include
        • anandamide [arachidonylethanolamide], which acts on CB1 receptors
        • 2-arachidonyl glycerin (2AG), which acts on CB2 receptors
      • enzymes and uptake systems involved in endocannabinoid metabolism and includes cyclooxygenase-2 (COX-2) and fatty acid amide hydrolase-1
    • References - 22305029Mayo Clin Proc 2012 Feb;87(2):172full-text, 24854329Epilepsia 2014 Jun;55(6):791full-text, and 23707385J Pain Symptom Manage 2013 Jul;46(1):142

Active ingredients

  • delta-9 tetrahydrocannabinol (THC) is main psychoactive cannabinoid found in cannabis, and is responsible for sensation of euphoria and feeling "high"3,4
    • THC concentrations have increased over time due to selective breeding and cultivation
      • concentrations of THC were 5% historically and now ≥ 30% in current samples, though concentrations vary widely among cannabis plants
      • mean concentration is about 11%
    • partial agonist activity at CB1 and CB2 receptors
    • noneuphoric effects include muscle relaxation, analgesia, antiemesis, psychosis, anxiety, and sedation
    • lethal overdose in humans has not been reported as THC spares autonomic nervous system (CB1 receptors nearly absent in brainstem)
    • may target transient receptor potential of vanilloid receptor type 1 (TRPV1) and type 2 (TRPV2)
  • cannabidiol is another important component of botanical cannabis
    • antagonist (inhibitor) at CB1 and CB2 receptors
    • inhibits metabolism of THC into its psychoactive metabolite 11-hydroxyTHC
    • has much lower psychoactive effects than THC
    • has fewer analgesic and antiemetic properties than THC
    • may act to potentiate THC's nonpsychoactive effects, by mitigating THC-associated anxiety and paranoia
    • may also have independent anxiolytic, antipsychotic, anticonvulsant, nonsedative, and neuroprotective properties
    • activates several other noncannabinoid systems including 5HT1a receptor, alpha3-3 and alpha-1 glycine receptors, transient receptor potential of ankyrin type 1 (TRPA1) channel, nuclear peroxisome proliferator-activated receptor gamma, TRPV1, and TPRV2
  • other nonpsychoactive cannabinoids of Cannabis sativa
    • include delta-9 tetrahydrocannabivarin (THCV) and cannabinol
    • less well-studied, but may interact with metabolism of endocannabinoids or with noncannabinoid receptors
  • References - 22305029Mayo Clin Proc 2012 Feb;87(2):172full-text, 24854329Epilepsia 2014 Jun;55(6):791full-text, and 23707385J Pain Symptom Manage 2013 Jul;46(1):142

Preparations

  • herbal cannabis (marijuana)
  • hashish3
    • solid or resinous preparation of glandular hairs from cannabis flowers, stalks, and leaves, which are separated from other plant parts resulting in "kief" powder, which is then compressed into blocks or bricks
    • THC concentrations up to 66% have been found in hashish
  • hash oil products (also called skunk, dab, wax, budder, butane hash oil, honey oil, shatter)1,3
    • consists of purification of hashish through dissolution of resin and filtering out remaining plant material; solvent evaporation results in hash oil
    • "dabbing" refers to use of hash oil in which a small amount (dab) is heated and the vapor inhaled
    • THC concentration may be as high as 81%
  • e-cigarette vaping paraphernalia can be used to ingest cannabis products (mnh26308021pcxh109128349pmdc26308021pInt J Environ Res Public Health 2015 Aug 21;12(8):9988full-text)
  • cannabis extracts and cannabis-derived formulations
    • generally contain both THC and cannabidiol to improve tolerability for medical uses by reducing psychoactive effects of THC
    • oral cannabis extract (Cannador)
      • laboratory-formulated to contain THC and cannabidiol at ratio of 2.5 mg:1.25 mg
      • not approved by FDA, Medicines and Healthcare Products Regulatory Agency in United Kingdom (MHRA), or European Medicines Agency (EMA)
    • nabiximols (Sativex)
      • cannabis-derived oromucosal spray containing THC 2.7 mg plus cannabidiol 2.5 mg in each spray
      • not available in United States, but available in Canada, United Kingdom, and Israel
      • approved in Europe for refractory spasticity in patients with multiple sclerosis (MS)
        • start with 1 spray (direct spray beneath tongue or inside cheeks, not toward pharynx) at bedtime
        • gradually increase dose over 2 weeks to a maximum of 12 sprays/day (for example, 1-2 sprays twice daily or 3 sprays daily)
        • other considerations for administration include
          • consistent timing between administration and mealtime as food may increase drug absorption
          • vary site of administration
          • inspect buccal mucosa regularly for signs of irritation due to excipients (such as ethanol and propylene glycol)
      • most common adverse effects of nabiximols include application site reactions such as, oral stinging and dry mouth, and intoxication-type effects; other adverse events may include dizziness, nausea, fatigue
      • see also Sativex in electronic Medicines Compendium (eMC) and Health Canada Apr 2005
    • cannabidiol extracts
      • delivered by aerosolization, vaporization, transdermally, or orally in oil-based capsule in research trials
      • has preferential distribution to fat, which may lead to accumulation with chronic administration (for example in patients with high adiposity)
      • no significant side effects in central nervous system or on vital signs after acute or chronic administration
      • pharmacokinetics and toxicity of cannabidiol in children not well understood

Pharmacokinetics

  • route of ingestion affects rate of cannabinoid absorption1,3
    • if smoking or vaping cannabis product
      • typically 35% of delta-9 tetrahydrocannabinol (THC) is bioavailable, though bioavailability of THC depends on the depth of inhalation, puff duration and breath-hold
      • mean time to peak serum concentration is 8 minutes, and peak concentration depends on dose
      • plasma levels decrease to 1-4 ng/mL by 3-4 hours after inhalation (there is minimal psychoactive effect at these levels)
      • fatigue, slowed thinking, and slowed recall may persist for up to 24 hours after use
    • when orally ingesting cannabis product
      • THC absorption is unpredictable due to gastric acid and first-pass liver metabolism; estimated 4%-20% of THC is bioavailable
      • mean time to peak serum concentration is between 2-4 hours, and psychotropic effects are reported to peak at 2-3 hours
      • depending on dose and specific effect, psychotropic effects of orally ingested cannabis may last for 4-12 hours
      • intoxication effects more unpredictable
    • rectal administration
      • bioavailability of THC rectally is reported to be about twice as high as that of orally ingested THC, due to higher absorption and lower first-pass metabolism
      • in 2 patients prescribed THC 2.5- to 5-mg rectal suppositories for spasticity, maximum plasma concentration of 1.1-4.1 ng/mL was reached within 2-8 hours
    • References - 17712819Chem Biodivers 2007 Aug;4(8):1770full-text, mnh12648025paph9353145pa9h9353145pbyh9353145pbeh9353145pbmh9353145pmdc12648025pClin Pharmacokinet 2003;42(4):327, 26540327Cleve Clin J Med 2015 Nov;82(11):765full-text3
  • oral ingestion of dronabinol
    • pharmacokinetics vary between capsule and oral solution
    • peak concentrations occur 1 hour after ingestion of oral solution and 2-4 hours after capsule
    • bioavailability 10%-20%
    • half-life 5.6 hours with oral solution and 19-36 hours with capsule
    • see Dronabinol topic for additional information
  • oral ingestion of nabilone
    • peak concentration 2 hours after ingestion
    • bioavailability 95.6%-100%
    • half-life 2 hours
    • see Nabilone topic for additional information

References

General references used

  1. Winstock AR, Ford C, Witton J. Assessment and management of cannabis use disorders in primary care. BMJ. 2010 Apr 1;340:c1571
  2. Sherman BJ, McRae-Clark AL. Treatment of Cannabis Use Disorder: Current Science and Future Outlook. Pharmacotherapy. 2016 May;36(5):511-35full-text
  3. Rella JG. Recreational cannabis use: pleasures and pitfalls. Cleve Clin J Med. 2015 Nov;82(11):765-72full-text
  4. Copeland J, Pokorski I. Progress toward pharmacotherapies for cannabis-use disorder: an evidence-based review. Subst Abuse Rehabil. 2016;7:41-53full-text

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  • DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. T912430, Cannabis Use; [updated 2018 Nov 30, cited place cited date here]. Available from https://www.dynamed.com/topics/dmp~AN~T912430. Registration and login required.

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