Accurate Education – Marijuana (Cannabis): Medical Use Overview

Marijuana (Cannabis)

The medical information on this site is provided as a resource for information only, and is not to be used or relied upon for any diagnostic or treatment purposes and is not intended to create any patient-physician relationship.  Readers are advised to seek professional guidance regarding the diagnosis and treatment of their medical concerns.

 

Marijuana: Medical Use Overview

The use of marijuana for medical purposes remains highly controversial and is compromised by a lack of good quality evidence regarding the specifics of clinical effectiveness and the details of treatment, including dosing amount, frequency and duration. The following information is provided as an introduction to what is believed to be true about medical uses of marijuana and/or its constituents.

 

Terminology

Cannabis:

The terms “cannabis” refers to marijuana the plant, including the varieties Cannabis Sativa and Cannabis Indica, as well the cannabis variety known as hemp, a variety of Cannabis with very low THC content cultivated for non-drug use.

Medical Marijuana:

This term is in popular use but it is imprecise.  It generally refers broadly to dried marijuana (cannabis) dispensed or otherwise obtained and used either for supervised medical purposes or for self-medication. The term can also be used to refer to the physician-recommended use of cannabis-based products to treat disease or improve symptoms.

Prescription Cannabinoids

Cannabinoids are compounds found in the marijuana plant and are the most abundant constituents used for medical purposes. The term “prescription” as related to cannabis-based products is limited to FDA-approved medications that require a prescritption from a physician. The term “prescription cannabinoids” refers to products containing one or more marijuana plant-derived or synthetically manufactured cannabinoids that are available by prescription only. Currently in the U.S. only three prescription cannabinoid medications are FDA-approved and legal to be prescribed in all states.

 

Cannabis-based products containing more than 0.3% THC are now legal for medical use in Louisiana but require specific written “recommendations” (not “prescriptions”) from a Louisiana-certified physician. These “recommended” medical marijuana-based products in Louisiana are not FDA-approved and are not covered by insurance. Furthermore, the possession of these products may not be legal in other states.

 

Pharmaceutical Cannabis-Based Products:

The term “pharmaceutical cannabis” refers to products that are derived from the marijuana plant and manufactured under controlled commercial conditions. Which of these products are available without a prescription varies state by state and the quality of manufacturing may also vary significantly from one product to another, with little to no regulatory oversight over the manufacturing process.

 

In Louisiana, the only pharmaceutical cannabinoid currently legal and available without a prescription or legal “recommendation” is cannabidiol (CBD), and only if it is 100% pure and manufactured from cannabis (hemp) stems or seeds, not leaves or flowers. While technically this is true, it appears that cannabis-based products derived from either whole plant or aerial (above ground) parts of the plant are available OTC locally as long as their THC content is <0.3%.

 

See:

Marijuana – Legislative Update for Louisiana

“Medical Marijuana” – Getting Started

Marijuana (Cannabis): Potential for Harm 

Marijuana (Cannabis): Side Effects and Drug Interactions

Combating Cannabis-Induced Anxiety, Panic and Paranoia

Marijuana (Cannabis): Dosing

Marijuana (Cannabis) – Dosing: “Pot” vs. Pharmaceutical Products

  

Cannabinoid-Based Medications:

Over-the-Counter Cannabinoid Medications:

 

Palmitoylethanolamide (PEA)

Palmitoylethanolamide (PEA)

 

Cannabidiol (CBD)

Cannabidiol (CBD) – Introduction

Cannabidiol (CBD) – Clinical Use and Dosing

Cannabidiol (CBD) – Drug Actions & Interactions

 

Prescription Cannabis-Based Medications:

FDA-Approved Prescription Cannabis-Based Medications

Louisiana-Rx Cannabis-Based Products – “Medical Marijuana”

 

Clinical Applications of Cannabis:

Cannabis – Anxiety (coming soon)

Cannabis – Chronic Pain Overview

Cannabis – Fibromyalgia

Cannabis – Headaches (coming soon)

Cannabis – Inflammatory Bowel Disease (coming soon)

Cannabis – Neuroinflammation (coming soon)

Cannabis – Sleep (coming soon)

 

The Medical Science of Cannabis:

The Endocannabinoid System

Marijuana (Cannabis) – THC Pharmacokinetics

Marijuana – Cannabinoids and Opioids

 

Understanding Marijuana Products

Marijuana – Botanical

Marijuana vs. Hemp

Marijuana – Ingestible (Orals & Edibles) coming soon

Marijuana – Inhaled (Smoked and Vaporized)

Marijuana – Topicals coming soon

 

Cannabinoids:

Cannabidiol (CBD)

Cannabigerol (CBG) (coming soon)

Cannabinol (CBN) (coming soon)

Tetrahydrocannabinol (THC) (coming soon)

Tetrahydrocannabivarin (THCV) (coming soon)

 

 Terpenes:

Terpenes – An Overview

   

See also:

Marijuana – Discontinuing Use

Marijuana Addiction – Cannabis Use Disorder (CUD)

  

 

Key to Links:

Grey text – handout

Red text – another page on this website

Blue text – Journal publication

cannabis-caduceus

This section is frequently updated for accuracy and completeness.

 

MarijuanaPotential for Therapeutic Benefit

There is currently a great deal of attention, both nationally and internationlly, on the potential medical benefits of marijuana (cannabis). The reasons for this attention are multiple, not the least of which is financial. That being said, however, there is a massive interest in therapeutic cannabis. One major reason for this is medical science’s interest in how cannabis offers medical benefits.

 

Patients have many reasons to advocate for use of cannabis and cannabinoids. These include the inadequate success of currently available pain therapies, skepticism about the pharmaceutical industry, anecdotal and media reports reporting the effectiveness of marijuana, familiarity with marijuana because of past recreational use and knowledge that marijuana has been used for millennia for medical purposes.

 

The evaluation of cannabis has led to a grand new arena of knowledge surrounding a new neuroendocrine system in humans and animals not previously known and even now still very poorly understood, But this new world surrounding cannabis is huge. The “endocannabinoid system,” explained further below, is present throughout the brain, central nervous system and all other organ systems. It represents an extremely important new field of study for understanding how our bodies work and it offers an excciting new world of therapeutic possibilities. It is a new frontier in medical science.

 

Our current understanding of medical uses of cannabis are, unfortunately, based on only a rudimentary beginning of research with little definitive knowledge established. The nature of the research currently available to the medical community to direct clinicians toward safe and effective therapeutic applications of cannabis  is very limited and based mostly on observational studies which provide very limited useful information to guide cannabis prescribing.

 

Cannabis – Research Studies

Observational studies are those in which data is reviewed by an investigator who observes and evaluates test subjects without manipulation or intervention and draws inferences from a population where no independent variables are under the control of the researcher. Observational studies can determine if there are associations between an activity and an outcome but cannot identify or confirm cause and effect. This is in contrast to randomised controlled trials (RCTs) where investigators do intervene by establishing specific variables to study and evaluate the effects of the intervention on an outcome. Randomised controlled trials are useful in determining causal relationships between treatment and outcome such as whether a medication actually works for a particular conditi0n. There are few and inadequate randomised controlled trials (RCTs) regarding marijuana to provide specifics for establishing treatment protocols.

 

There are many preclinical studies (animal and labatory-based research) that have shown that modulating the endocannabinoid system (ECS) with cannabinoids may be effective for mood and anxiety disorders, movement disorders, neuropathic (nerve) pain, epilepsy, multiple sclerosis, spinal cord injury, cancer, atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity/metabolic syndrome, insomnia, drug addiction, Alzheimer’s disease, and osteoporosis.  Unfortunately, there remains a lack of good quality human-based research to confirm the specifics of what the preclinical studies suggest. Most human research has focused on chronic pain, muscle spasticity, nausea, vomiting and anorexia. Some conditions, such as migraine headaches, fibromyalgia, and Irritable Bowel Syndrome (IBS) have underlying physiological patterns that suggest an underlying endocannabinoid deficiency, suggesting they may be effectively treated with cannabinoid medicines.

 

The Endocannabinoid System (ECS): Endocannabinoids and Phytocannabinoids

There are a number of physiologically active constituents of the cannabis (marijuana) plant, some of which have shown therapeutic benefits in a broad range of conditions. The major group of compounds found to be uniquely abundant in cannabis is the “cannabinoids.”  Originally thought to be unique to cannabis, naturally occuring cannabinoids (endocannabinoids) were subsequently discovered in humans and animals (all vertebrates). An entire endocannabinoid system consisting of multiple types of endocannabinoids and cannabinoid receptors is distributed throughout the body.

 

This endocannabinoid system (ECS) of endocannabinoid receptors and endocannabinoids is similar to the opioid system of opioid receptors and the naturally occuring opioids (endorphins) in the body. The ECS regulates many physiologic functions ranging from the immune system to the nervous system and impacts sleep, appetite, mood, pain and other functions. For this reason, marijuana has attracted a great deal of attention from a pharmacotherapy perspective for its potential to affect many physiologic functions with possible benefit. 

 

The clinical benefits from marijuana are derived from the many chemical agents found in the plant, including more than 100 pharmacologically active constituents, including cannabinoids and terpenes. The two best understood and most common of the cannabinoids are THC (tetrahydrocannabinol) and CBD (cannabidiol). There is very limited scientific information on the pharmacology and toxicology of the other constituents found in cannabis. It is believed that the clinical effects of marijuana come from not just THC or CBD, but are determined by both the concentrations and ratios of these two constituents as well as influences from the many other cannabinoids and terpenes found in the plant.

 

THC (tetrahydrocannabinol)

THC use is applicable for many symptoms and conditions including pain, nausea, spasticity/spasms, appetite stimulation, anxiety, depression, post-traumatic stress disorder (PTSD) and insomnia. THC and its active metabolite, 11-Hydroxy-THC. produce the “high” or euphoria associated with use of marijuana.

 

CBD (cannabidiol)

CBD does not produce the mind-altering “high” effects like euphoria but it does reduce anxiety and enhance sleep. CBD is a versatile anti-inflammatory analgesic, operating through numerous distinct mechanisms. It has anti-convulsant, anti-psychotic, antioxidant, neuroprotective and immunomodulatory effects. CBD is also thought to reduce nausea, particularly related to chemotherapy. In combination with THC, CBD modulates some of the side effects of THC, including reducing THC-induced anxiety. CBD suppresses the “high” caused by THC when provided at an 8:1 CBD:THC ratio.

See: Cannabidiol (CBD) – Introduction

  

Marijuana – Potential for Harm

While there is great hope for the therapeutic potential of cannabis, it is not for everyone and certain groups have been identifid who should likely avoid use of cannabis. The following groups are believed to be potentially at increased risk of harm from use of cannabis:

 

  1. Children, adolescents, and young adults (<25 y/0)

  2. Women who are pregnant or breastfeeding

  3. Those with a personal or family history of psychotic disorders such as schizophrenia

  4. Those with a history of chronic lung disease, cardiovascular disease and/or kidney disease

  

For more information: Marijuana (Cannabis): Potential for Harm 

  

 

Clinical Evidence for Effectiveness

Research on Medical Marijuana

Definitive research regarding the medical uses of marijuana and its constitutents remains limited and in only early stages. Observational studies are those in which data is reviewed by an investigator who observes individuals without manipulation or intervention and draws inferences from a population where no independent variables are under the control of the researcher. Observational studies can determine if there are associations between an activity and an outcome but cannot identify or confirm cause and effect. This is in contrast to randomised controlled trials (RCTs) where investigators do intervene and look at the effects of the intervention on an outcome. RCTs are useful in determining cause-effect relationships between treatment and outcome such as whether a medication actually works for a particular conditi0n.. The current state of medical marijuana research is based mostly in observational studies with very few RCTs to guide management of most medical conditions with specific cannabis-based treatments.

 

Based on the 2017 report from the National Academies of Sciences, Engineering, and Medicine there is conclusive or substantial evidence that cannabis or cannabinoids are effective for the treatment of:

 

  1. Chronic pain in adults
  2. Chemotherapy-induced nausea and vomiting
  3. Multiple sclerosis spasticity symptoms

 

 

The report also found moderate evidence that cannabis or cannabinoids are effective for:

 

  1. Improving short-term sleep outcomes in individuals with sleep disturbance associated with obstructive sleep apnea syndrome (See: Sleep Apnea)
  2. Fibromyalgia
  3. Spasticity associated with Multiple Sclerosis

 

 

Additionally, there is increasing but limited research showing that cannabinoids are safe and effective in the treatment of:

 

  1. Seizure disorders
  2. Increasing appetite and decreasing weight loss associated with HIV/AIDS
  3. Tourette syndrome
  4. Several geriatric conditions
  5. Anxiety, particularly in individuals with PTSD and social anxiety disorder
  6. Depression, associated with chronic pain
  7. Neurocognition in some cases of dementia

 

 

Relative Contraindications to Cannabis Use: 

  1. Patients who are <25 years of age
  2. Patients who have a current, past, or strong family history of psychosis
  3. Patients who have a current or past cannabis use disorder (marijuana addiction)
  4. Patients who have a current substance use disorder (chemical or behavioral)
  5. Patients who have cardiovascular or respiratory disease
  6. Patients who are pregnant or planning to become pregnant
  7. Inhaled cannabis should be used with caution in patients who smoke tobaccco

 

Precautions:

  1. Patients who are at increased risk of cardiovascular disease
  2. Patients who have anxiety or mood disorders
  3. Patients who are taking opioids or benzodiazepines

 

Harm Reduction:

  1. Do not operate dangerous equipment or perform potentially dangerous activities after cannabis use
  2. Do not use with alcohol, opioids, or sedating drugs, especially benzodiazepines (Valium, Xanax, Klonopin etc)
  3. Keep cannabis-based products safely stored under lock and key
 

Driving:

Cannabis users should be advised not to drive for at least:

(1) Three to four (3 to 4) hours after smoking

(2) Four – six (4-6) hours after sublingual administration

(3) Six – eight (6-8) hours after oral ingestion

(4) Eight (8) hours if they experience a subjective “high”

 

THC serum concentrations of 2–5 μg/L have been shown to impair driving, and concentrations of 7–10 μg/L can produce impairment equivalent to a blood alcohol concentration of 0.05%. Sweden and Australia have zero tolerance for illegal drugs in drivers. Of those drivers convicted for impaired driving in Sweden, 90% had blood levels of THC <5-μg/L and 61% had blood levels of THC <1 μg/L.

 

Two states, Nevada and Ohio, have set blood limits of ≥2 μg/L for THC or ≥5 μg/L for THCCOOH (a primary metabolite of THC) and Colorado has set(?) a limit of 5.0 μg/L THC in blood.. The highest limits in Europe are 3 μg/L for THC in Portugal and 50 μg/L for THCCOOH in Poland. While existing laws focus on THC and THCCOOH concentrations, appropriate cutoffs might also be selected for 11-OH-THC (another primary metabolite of THC)  due its shorter detection window. THC- glucuronide, cannabinol, and cannabidiol concentrations in blood may also indicate recent cannabis smoking.

 

Of note, cannabinoids may be detected in the blood of chronic daily cannabis smokers for greater than one month after sustained abstinence. This is consistent with the time course of persisting neurocognitive impairment reported in recent studies. There is a strong public safety need to reduce cannabis-impaired driving  and reduce cannabis-related motor vehicle injuries and deaths.

  

Dosing

See:

Louisiana-approved Recommended Cannabis-Based Products – “Medical Marijuana”

FDA-approved Prescription Cannabis-Based Products

Cannabidiol (CBD) – Clinical Use and Dosing

 

With as many as 850 brands of marijuana-derived CBD products and 150 hemp-derived products on the market and an even greater number of various extracts of THC and marijuana plants cultivated to produce maximum THC concentration, universal dosing recommendations are nearly impossible.

 

The determination of dosing is one of the major stumbling blocks in the study of medical marijuana. This is because marijuana, a plant, varies widely in the amount and ratios of the pharmacologically active constituents present depending on a multitude of variables. Depending on the plant there may be over 100 pharmacologically active constituents all of which vary depending on the genetics of the plant, the conditions in which the plant was grown, how and when it was harvested and other variables. As such there is a huge variability in the potency and expected effects between different plants.

 

As noted above, the major pharmacologically active cannabinoids in marijuana are THC and cannabidiol (CBD). The average contents of THC and CBD in dried plant preparations of marijuana confiscated from 1993 to 2008 in the United States were 4.5 and 0.4, respectively, although these contents vary widely. In the last decade these percentages have increased in different strains to more than 3-5 times as potent or more:

 

  1.  THC levels doubled (8.9% in 2008, 17.1% in 2017)
  2.  CBD levels decreased from 0.37% in 2008 to 0.14% in 2017
  3.  THC:CBD ratio increase from 23:1 in 2008 to 104:1 in 2017

    

The significance of these numbers is that they indicate a very different product from the marijuana older people may remember from the days they used marijuana recreationally 20-30 years ago and now are turning to contemporary marijuana use for medical purposes. The higher THC content is associated with more side effects such as anxiety, impaired thinking and other symptoms associated with higher THC dosing. Additionally, the reduced amount of CBD, which reduces THC side effects, further contributes to the greater likelihood of side effects. This calls for careful dosing, starting at low doses and increase dosing slowly as indicated.

 

Because Louisiana law does not permit the use of raw or dried marijuana plant for medical purposes, dosing is not covered here. Other countries guidelines are briefly reviewed below but may not be up to date.

 

Canadian Guidelines – 2014

Based on Canadian guidelines published in 2014, smoked cannabis might be indicated for patients with severe neuropathic pain conditions who have not responded to adequate trials of pharmaceutical cannabinoids and standard analgesics. Smoked cannabis is contraindicated in patients who: (1) are 25 years of age or younger; (2) have a current, past, or strong family history of psychosis; (3) have a current or past cannabis use disorder (marijuana addiction); (4) have a current substance use disorder (addiction to other drugs); (5) have cardiovascular or respiratory disease; or (6) are pregnant or planning to become pregnant. It should be used with caution in patients who smoke tobacco, who are at increased risk of cardiovascular disease, who have anxiety or mood disorders, or who are taking high doses of opioids or benzodiazepines.

 

Based on these Canadian guidelines, when smoking is advised (which it is generally not), initial dosing recommendations for smoked marijuana are usually for small amounts of lower-potency marijuana. For example, the starting recommended dosing is 1 inhalation of a 9% maximum THC “joint” once per day. This can be increased to a maximum recommended dose of 1 inhalation 4 times a day, resulting in approximately half a “joint” per day (or 400 mg). Patients should not operate dangerous equipment or perform potentially dangerous activities after use. This includes no driving for 3 to 4 hours after inhaled medical marijuana, 6 hours after oral ingestion, and for at least 8 hours if they experience a subjective “high.”

 

Higher doses are sometimes used. It should be noted that if patients use a 5 gram dose of 15% THC, this represents approximately a 20 times higher dose than the recommended 400 mg of 9% THC. Higher doses, especially at this level are associated with significantly higher risk of adverse side effects (see below). In marijuana resin (commonly referred to as hash or hashish), the average contents of THC, CBD, and CBN are 14.1, 2.5, and 1.9%, respectively. Other commercial products including oils and edibles may contain even higher potencies.

 

Germany

In Germany currently there are 14 types of cannabis flowers that can be prescribed, with THC concentrations varying between 1% and 22% and CBD concentrations varying between 0.05% and 9%. Dosing information for specific indications is not available but the German Narcotic Drugs Act sets the maximum amount that can be prescribed within a 30-day period at 100 g cannabis in form of flowers, regardless of THC content. While  THC-containing capsules and oil are not permitted under the German Narcotic Drugs Act, they can be prescribed for individual therapeutic trials as compounded medications in the form of drops, capsules or inhalation solution. Apparently, their recommended daily doses of THC range between 5 and 30 mg.

    

Adverse Side Effects

Overall, the adverse side effects of medical cannabis are within the range tolerated for other common medications. Multiple studies have demonstrated that there is no higher incidence of serious adverse events in cannabis subjects following medical cannabis use compared with control subjects, although non-serious adverse events were significantly higher in cannabinoid groups. Dizziness is the most common non-serious adverse effect reported. Other common adverse effects include:

 

  1. Euphoria, altered consciousness
  2. Acute panic or paranoid reaction
  3. Altered motivation
  4. Impaired attention, memory, and psychomotor performance
  5. Tachycardia, orthostatic hypotension (drop in blood pressure associated with sitting to standing)
  6. Dry mouth
  7. Increased appetite

  

For more information about cannabinoids and their side effects:

Marijuana (Cannabis): Side Effects and Drug Interactions

 

Cognitive impairment, including the ability to learn and remember new information, has been associated with long term illicit cannabis use but has been shown to be reversible after a period of abstinence.

 

Long-term heavy cannabis smokers have increased risk of pulmonary symptoms such as chronic bronchitis and COPD but have no increased incidence of lung cancer

 

As expected, cannabis-naive patients tend to have more frequent adverse side effects compared with regular users. The effects of THC can change over time, with therapeutic effects more resistant to tolerance development than adverse side effects. Careful attention. to appropriate dosage, delivery method, and ratio of cannabinoids can reduce many of the adverse side effccts.

 

It is important to point out that the adverse effects of medical cannabis cannot be equated with the adverse effect of illicit marijuana use. The amounts and ratios of the different cannabinoid constituents vary dramatically between different marijuana plants, whereas medical marijuana is anticipated to be formulated with specific standardized doses and ratios of the different cannabinoid components. The use of illicit marijuana does not allow for any accurate prediction of dosing.

 

Interactions With Other Drugs and Herbal Preparations

Cannabinoids and Opioids

There appears to be a synergistic analgesic (pain-relieving) benefit when cannabinoids are added to opioids for treatment of pain in which there is a greater-than-additive benefical effect with the addition of cannabinoids. Studies indicate a trend towards reduced use of opioids when patients taking opioids add cannabinoids to their regimen. It is not uncommon for patients started on cannabinoids to be able to taper off opioids.

 

Additionally, animals studies suggest that cannabinoids may reduce the development of tolerance to the analgesic benefits of opioids, resulting in less need for opioid dose escalation.

 

There is no enhancement of cardiorespiratory suppression from opioids with the addition of cannabanoids due to the very low density of cannabinoid (CB) receptors in brainstem cardiorespiratory centers. Cannabinoids are not reported to have any significant effecct on opioid metabolism, however there does appear to be a potential to do so (See below).

For more information, See Cannabinoids and Opioids

  

Alcohol and Benzodiazepines

The combination of cannabinoids with alcohol and benzodiazepines may increase sedation and cognitive impairment.

 

NSAIDS (Non-Steroid Anti-inflammatory Drugs)

NSAIDs such as ibuprofen and naproxen, particularly indomethacin, may suppress the effects of THC.

 

 Anticholinergic drugs (Tricyclic antidepressants (TCAs) and some muscle relatxers)

Medications with anticholinergic activity such as amitriptyline (Elavil) and doxepin, and muscle relaxers such as cyclobenzaprine (Flexeril) may increase the psychoactive side effccts of cannabinoids.

 

Herbal Preparations

Sedative agents such as sleep aids (includes supplements containing GABA, melatonin, 5-HTP, skullcap, or valerian) – Use caution when taking these products and cannabis products together because of the potential for increased drowsiness.

 

Drug Metabolic Interactions

The major cannabanoids, THC and CBD are both metabolized in the liver by the CYP450 enzymes 2C9 and 3A4. Drugs that inhibit these enzymes may enhance or prolong the effects of THC and CBD. Whether people with genetic variants of these enzymes may experience altered effects from cannabinoids is not certain. 

For more information about cannabinoids and interactions with other drugs and herbal supplememts:

Marijuana (Cannabis): Side Effects and Drug Interactions

 

Costs

In Loisiana, the cost of recommended cannabis-based products ranges from about $100-200/month or more, depending on dosing amounts and ratios of constituent cannabinoids.

 

As of February, 2018, medical marijuana prices from licensed producers in Canada ranged from $4.25 to $15 per gram. Public Safety Canada reports the average price from licensed producers to be $8.37 per gram. Given that most patients smoke 1 to 3 g per day (compared to the recommended 400 mg per day), typical costs are approximately $250 to $750 per month.

 

Botanical Cannabis

Botanical cannabis is highly inconsistent and variable in its chemical composition. Some authorities describe Cannabis as a single species, while others describe up to four separate species: Cannabis sativa, Cannabis indica, Cannabis ruderalis, and Cannabis afghanica (or kafiristanica). Cannabis likely evolved in Central Asia, native to regions including Afghanistan, Pakistan, India and China.  Cannabis species have been found to fall into three general chemotypes (chemical compositions) based on genetically-determined THC:CBD ratios:

Category I: Relatively high total THC and low total CBD

Category II: THC:CBD ratios near equal (1:1)

Category III: Relatively low total THC and high total CBD

 

While native Central Asian cannabis is mostly chemotype III (CBD- dominant), emerging commercial cannabis over the last few decades such as currently grown in Washington are more likely to fall into chemotype I (THC- dominant). While there still are biochemically distinct strains of Cannabis, the Cannabis sativa amd Cannabis indica distinction is commonly debated in the laymen’s literature with alleged differences in their constituent combinations and therapeutic effects. Sativa is often described as being uplifting and energetic, whereas indica as being relaxing and calming.

There are thousands of individual cannabis types, which people often erroneously refer to as ‘strains’, whereas the preferred term is chemical variety or ‘chemova.r’  Each chemovar contains varying concentrations of cannabinoids and other constituents with important pharmacological and modulatory effects. These constituents include the monoterpenoids [myrcene (analgesic, sedating), limonene (anti- depressant and immune-stimulating), pinene (acetylcholinesterase inhibitor alleviating short-term memory impairment from THC) and the sesquiterpenoid beta-caryophyllene (anti-inflammatory analgesic and selective full agonist at the CB2 receptor.

At this time, however, due to the evolution of commercial breeding the distinction between the two, as one expert put it “is total nonsense and an exercise in futility.” One can no longer assess the biochemical content of a given Cannabis plant based on its height, branching, or leaf morphology. Due to the degree of interbreeding and hybridization, currently only a biochemical assay can accuratey identify what the cannabinoid profile for a plant really is.

 

However, no universal standards for laboratory testing protocols currently exist, and there is controversy as to whether all reported results are legitimate. A 2018 study investigated the consistency of reported cannabinoid content of legal cannabis products from state-certified laboratories in Washington. The study  documented significant differences in the cannabinoid content reported by different laboratories. It was reported that there is relative stability in cannabinoid levels of commercial flower and concentrates over time. This publication underscores the need for standardized laboratory methodologies in the legal cannabis industry to provide a framework for quantitatively assessing laboratory quality.

 

THC and CBD concentrations depend not only on the species and strain, but also cultivation, growth conditions, harvesting and storage of the plant. The average contents of THC, CBD, and CBN in dried plant preparations of marijuana confiscated from 1993 to 2008 in the United States were 4.5, 0.4, and 0.3%, respectively, although these contents varied widely. In marijuana resin, commonly referred to as hash or hashish, the average contents of THC, CBD, and CBN are 14.1, 2.5, and 1.9%, respectively. However, in the decade following 2008, various strains and marijuana-based products contain substantially higher contents of these constituents, especially THC which can range upwards of 20-30% or more.

 

Aside from the increasing number of CBD predominant strains introduced in the market recently, almost all cannabis currently are high-THC strains. While the strength and ratio of THC and CBD play a large role in the clinical effects of marijuana, a synergy exists between these two components and their combination with other constituents that produce effects that are uniquely determined by the amount and ratios of all the constituents. In addition to THC and CBD, there are other cannabinoids in cannabis including tetrahydrocannabivarin (THCV), cannabigerol (CBG) and cannabichromene (CBC), as well as other pharmacologically active chemical constituents including cannabis terpenoids that impact the clinic effects of marijuana.

 

Cannabis terpenoids include limonene, myrcene, a-pinene, linalool, b-caryophyllene, caryophyllene oxide, nerolidol and phytol. These terpenoids are derived from a shared precursor with the cannabinoids, and are all flavour and fragrance components common to human diets that have been designated “Generally Recognized as Safe” by the FDA. Terpenoids are quite potent and affect behaviour when inhaled even at very low levels. Terpenoids have unique therapeutic effects that likely contribute to the synergy or “entourage” effects of cannabis with respect to treatment of pain, inflammation, depression, anxiety, addiction, epilepsy, cancer and infections.

 

In all likelihood, the differences in observed effects in Cannabis are due to their terpenoid content, which is rarely assessed or reported to potential consumers. The sedation of the so-called “indica” strains is often wrongly attributed to CBD content when, in fact, CBD can be stimulating in low and moderate doses. Rather, sedation in most common Cannabis strains is attributable to their myrcene content, a monoterpene with a strongly sedative effect that resembles a narcotic. In contrast, a high limonene content (common to citrus peels) will be uplifting on mood, while the presence of the relatively rare terpene in Cannabis, alpha-pinene, can effectively reduce or eliminate the short-term memory impairment classically induced by THC.

 

This complexity of cannabis constituents and their pharmacologic impact underscores the importance of pharmaceutical medical marijuana in which pharmacologic agents are manufactured with specific doses and ratios which allow for safer titration of dosing to achieve desired clinical benefits.

 

Resources:

National Academy of Sciences

The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research

 

International Cannabinoid Research Society

International Cannabinoid Research Society – Home page

 

You Tube video marijuana education links:

Cannabis The Evil Weed (2009) part 1 of 16

 

 

  1. Introduction to Medical Cannabis (Module 1) – The Endocannabinoid System by Dr. Towpik
  2. Introduction to Medical Cannabis (Module 2) – Pharmacology & Phytocannabinoids by Dr. Towpik
  3. Introduction to Medical Cannabis (Module 3) – Chronic Pain, Palliation & Case Studies by Dr. Towpik
  4. Introduction to Medical Cannabis (Module 4) – CINV & Epilepsy by Dr. Teh
  5. Introduction to Medical Cannabis (Module 5) – Adverse Effects & Potential Drug Interactions
  6. Introduction to Medical Cannabis (Module 6) – Patient Care, Dosing & Titration by Dr. Teh

 

 

Lay-person Websites

These lay-person websites appear to be good resources for exploring medical marijuana. However, as is the case generally regarding medical applications of marijuana and its constitnuents, there is a huge amount of information that is not based in good science and relies on anecdotal (word-of-mouth) evidences. Reader, beware:

 

  1. www.CannabisBusinessTimes.com
  2. www.CBDschool.com
  3. www.gfarma.news
  4. www.GreenCamp.com
  5. www.Healer.com
  6. www.Marijuana.com
  7. www.MedicalJane.com
  8. www.profofpot.com
  9. www.ProjectCBD.org
  10. www.Weedmaps.com

 

References:

Medical Marijuana – Louisiana-approved medical conditions

  1. Approved Medical Conditions in Louisiana – May 16, 2019 Articles Supporting Recommendations

Medical Marijuana – Louisiana-approved medical marijuana products

  1. GB Sciences Louisiana Product Guide (07.23.2019)

Politics of Medical Marijuana – Consequences

  1. Use-of-Prescription-Pain-Medications-Among-Medical-Cannabis-Patients
  2. Effects of Legal Access to Cannabis on Scheduled II-V Drug Prescriptions. – PubMed – NCBI
  3. It is premature to expand access to medicinal cannabis in hopes of solving the US opioid crisis – 2018
  4. Association of Medical and Adult-Use Marijuana Laws With Opioid Prescribing for Medicaid Enrollees. – PubMed – NCBI
  5. Patterns of medicinal cannabis use, strain analysis, and substitution effect among patients with migraine, headache, arthritis, and chronic pain in a medicinal cannabis cohort – 2018
  6. Patterns and correlates of medical cannabis use for pain among patients prescribed long-term opioid therapy. – PubMed – NCBI
  7. Associations between medical cannabis and prescription opioid use in chronic pain patients – A preliminary cohort study – 2017
  8. The prevalence and significance of cannabis use in patients prescribed chronic opioid therapy: a review of the extant literature. – PubMed – NCBI
  9. The use of cannabis in response to the opioid crisis: A review of the literature. – PubMed – NCBI
  10. Medical Cannabis Laws and Opioid Analgesic Overdose Mortality in the United States, 1999–2010 – 2014
  11. Rationale for cannabis-based interventions in the opioid overdose crisis – 2017
  12. Cannabis and the Opioid Crisis – 2018
  13. Impact of co-administration of oxycodone and smoked cannabis on analgesia and abuse liability. – PubMed – NCBI
  14. Building smart cannabis policy from the science up – 2017

Politics of Medical Marijuana – Louisiana

  1. louisiana-medical-marijuana-expansion-bill-signed-into-law-may-20-2016
  2. louisiana-2016-sb180-chaptered
  3. medical-marijuana-in-louisiana-who-will-get-access-june-2015
  4. now-in-effect-louisiana-medical-marijuana-law-shields-patients-and-caregivers-from-prosecution-aug-5-2016
  5. La house committee passes bill to allow medical marijuana prescription 4-5 2018

    

Politics of Medical Marijuana – Colorado

  1. The Clinical Conundrum of Medical Marijuana – 2017

Medical Marijuana – Prescribing Guidelines

  1. Simplified guideline for prescribing medical cannabinoids in primary care – Canadian Family Physician – 2018
  2. Physician Recommendation of Medical Cannabis Guidelines Calif Medical Assoc – 2011
  3. Prescribing smoked cannabis for chronic noncancer pain. Preliminary recommendationsCanadian Family Physician – 2014

 

Medical Marijuana – Potential Harms Associated with Cannabis Use

  1. Brief Review of Human Studies Regarding Increased Risk of Harm with Cannabis Use – State of Minnesota – 2016

 

Medical Marijuana – Driving

  1. Establishing legal limits for driving under the influence of marijuana – 2014
  2. Medical Marijuana and Driving – a Review – 2014
  3. Impact of Prolonged Cannabinoid Excretion in Chronic Daily Cannabis Smokers’ Blood on Per Se Drugged Driving Laws – 2013

 

Medical Marijuana – Opioids

  1. Use-of-Prescription-Pain-Medications-Among-Medical-Cannabis-Patients
  2. It is premature to expand access to medicinal cannabis in hopes of solving the US opioid crisis – 2018
  3. Patterns of medicinal cannabis use, strain analysis, and substitution effect among patients with migraine, headache, arthritis, and chronic pain in a medicinal cannabis cohort – 2018
  4. Patterns and correlates of medical cannabis use for pain among patients prescribed long-term opioid therapy. – PubMed – NCBI
  5. Associations between medical cannabis and prescription opioid use in chronic pain patients – A preliminary cohort study – 2017
  6. The prevalence and significance of cannabis use in patients prescribed chronic opioid therapy: a review of the extant literature. – PubMed – NCBI
  7. The use of cannabis in response to the opioid crisis: A review of the literature. – PubMed – NCBI
  8. Medical Cannabis Laws and Opioid Analgesic Overdose Mortality in the United States, 1999–2010 – 2014
  9. Rationale for cannabis-based interventions in the opioid overdose crisis – 2017
  10. Cannabis and the Opioid Crisis – 2018
  11. Impact of co-administration of oxycodone and smoked cannabis on analgesia and abuse liability. – PubMed – NCBI
  12. Cannabinoid–Opioid Interaction in Chronic Pain
  13. Synergistic interactions between cannabinoid and opioid analgesics. – PubMed – NCBI
  14. FDA approves CBD drug – Epidiolex – The Washington Post

Medical Marijuana – Opioid Drug Interactions

  1. The Effect of CYP2D6 Drug-Drug Interactions on Hydrocodone Effectiveness – 2014
  2. Cannabidiol, a Major Phytocannabinoid, As a Potent Atypical Inhibitor for CYP2D6 – 2011
  3. Potent inhibition of human cytochrome P450 3A isoforms by cannabidiol. – Role of phenolic hydroxyl groups in the resorcinol moiety – 2011

Medical Marijuana – Pain

  1. Use-of-Prescription-Pain-Medications-Among-Medical-Cannabis-Patients
  2. It is premature to expand access to medicinal cannabis in hopes of solving the US opioid crisis – 2018
  3. Patterns of medicinal cannabis use, strain analysis, and substitution effect among patients with migraine, headache, arthritis, and chronic pain in a medicinal cannabis cohort – 2018
  4. Patterns and correlates of medical cannabis use for pain among patients prescribed long-term opioid therapy. – PubMed – NCBI
  5. Associations between medical cannabis and prescription opioid use in chronic pain patients – A preliminary cohort study – 2017
  6. Medical Marijuana for Treatment of Chronic Pain and Other Medical and Psychiatric Problems – A Clinical Review – 2015

Medical Marijuana – Pharmacokinetics

  1. Human Cannabinoid Pharmacokinetics – 2007

    

Medical Marijuana – Product Evaluation

  1. The Cannabinoid Content of Legal Cannabis in Washington State Varies Systematically Across Testing Facilities and Popular Consumer Products – 2018
  2. Recommended methods for the identification and analysis of cannabis and cannabis products – 2009
  3. Quality Control of Traditional Cannabis Tinctures – Pattern, Markers, and Stability – 2016

 

Medical Marijuana – Sleep & Sleep Apnea

  1. Medical Cannabis and the Treatment of Obstructive Sleep Apnea – An American Academy of Sleep Medicine Position Statement – 2018
  2. Cannabis, Cannabinoids, and Sleep: a Review of the Literature. – PubMed – NCBI
  3. Misc Abstracts @ Obstructive Sleep Apnea – 2017
  4. Cannabinoid May Be First Drug for Sleep Apnea – 2018
  5. Pharmacotherapy of Apnea by Cannabimimetic Enhancement, the PACE Clinical Trial – Effects of Dronabinol in Obstructive Sleep Apnea – 2018
  6. Effectiveness of Raw, Natural Medical Cannabis Flower for Treating Insomnia under Naturalistic Conditions – 2019
  7. Effect of D-9-Tetrahydrocannabinol and Cannabidiol on Nocturnal Sleep and Early-Morning Behavior in Young Adults – 2004

Medical Marijuana – PTSD

  1. Cannabidiol as a Therapeutic Alternative for Post-traumatic Stress Disorder – From Bench Research to Confirmation in Human Trials – 2018
  2. Cannabidiol in the Treatment of Post-Traumatic Stress Disorder – A Case Series – 2019 
  3. Medicinal cannabis for psychiatric disorders – a clinically-focused systematic review – 2020

 

Medical Marijuana –Misc

  1. A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol and cannabidiol. – PubMed – NCBI
  2. Cannabis and cannabis extracts – greater than the sum of their parts? – 2001
  3. Medical cannabis and mental health: A guided systematic review. 2016 – PubMed – NCBI
  4. Epidemiological characteristics, safety and efficacy of medical cannabis in the elderly. – PubMed – NCBI
  5. Cannabis-conclusions – 2017 National Academy of Sciences
  6. Cannabis-chapter-highlights – 2017 National Academy of Sciences
  7. Cannabis-report-highlights – 2017 National Academy of Sciences
  8. Clinical Endocannabinoid Deficiency (CECD): Can this Concept Explain Therapeutic Bene ts of Cannabis in Migraine, Fibromyalgia, Irritable Bowel Syndrome and other Treatment-Resistant Conditions?-2004
  9. Cannabimimetic phytochemicals in the diet – an evolutionary link to food selection and metabolic stress adaptation? – 2016
  10. Marijuana use and the risk of lung and upper aerodigestive tract cancers: results of a population-based case-control study. – PubMed – NCBI
  11. Cannabis use and cognitive function: 8-year trajectory in a young adult cohort. – PubMed – NCBI
  12. Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. – PubMed – NCBI
  13. Cannabinoids and Cytochrome P450 Interactions. – PubMed – NCBI Pharmacogenetics of Cannabinoids – 2018
  14. Systematic review of systematic reviews for medical cannabinoids – 2018
  15. Adverse effects of medical cannabinoids – a systematic review – 2008
  16. Cannabimimetic effects modulated by cholinergic compounds. – PubMed – NCBI
  17. Antagonism of marihuana effects by indomethacin in humans. – PubMed – NCBI
  18. Pharmacokinetics and pharmacodynamics of cannabinoids. – PubMed – NCBI
  19. Clinical Pharmacodynamics of Cannabinoids – 2004
  20. Affinity and Efficacy Studies of Tetrahydrocannabinolic Acid A at Cannabinoid Receptor Types One and Two. – 2017
  21. Quality Control of Traditional Cannabis Tinctures – Pattern, Markers, and Stability – 2016
  22. Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review. – PubMed – NCBI
  23. Pharmacology of Cannabinoids
  24. Current-status-and-future-of-cannabis-research-Clin-Researcher-2015
  25. Taming THC – potential cannabis synergy and phytocannabinoid-terpenoid entourage effects – 2011
  26. The Cannabis sativa Versus Cannabis indica Debate – An Interview with Ethan Russo, MD – 2016
  27. Review of the neurological benefits of phytocannabinoids – 2018
  28. Alternatives to Opioids in the Pharmacologic Management of Chronic Pain Syndromes: A Narrative Review of Randomized, Controlled, and Blinded Clinic… 2017 – PubMed – NCBI
  29. The Effects of Cannabis Among Adults With Chronic Pain and an Overview of General Harms: A Systematic Review. – PubMed – NCBI – 2017
  30. Medical Cannabis for Older Patients—Treatment Protocol and Initial Results – 2019

Emphasis on Education

 

Accurate Clinic promotes patient education as the foundation of it’s medical care. In Dr. Ehlenberger’s integrative approach to patient care, including conventional and complementary and alternative medical (CAM) treatments, he may encourage or provide advice about the use of supplements. However, the specifics of choice of supplement, dosing and duration of treatment should be individualized through discussion with Dr. Ehlenberger. The following information and reference articles are presented to provide the reader with some of the latest research to facilitate evidence-based, informed decisions regarding the use of conventional as well as CAM treatments.

 

For medical-legal reasons, access to these links is limited to patients enrolled in an Accurate Clinic medical program.

 

Should you wish more information regarding any of the subjects listed – or not listed –  here, please contact Dr. Ehlenberger. He has literally thousands of published articles to share on hundreds of topics associated with pain management, weight loss, nutrition, addiction recovery and emergency medicine. It would take years for you to read them, as it did him.

 

For more information, please contact Accurate Clinic.

 

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