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.
The term “prescription cannabinoid” 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 cannabinoids are FDA-approved and legal to be prescribed in all states. These include:
- Cesamet (nabilone, a synthetic cannabinoid similar to THC) – Available in the U.S.
- Epidiolex (a plant-derived CBD) – Available in the U.S.
- Marinol (dronabinol, a synthetic THC) – Available in the U.S.
- Sativex (a combination of THC and CBD in a 1:1 ratio) is a prescription cannabinoid available in Canada and Europe but not yet FDA-approved or available in the U.S. Some of the most informative research into medical uses of marijuana has come from studies evaluating Sativex because it is plant-base and contains both THC and CBD as well as other pharmacologicaly significant cannabis plant constituents including some terpenes.
This term is in popular use but it is imprecise. It generally refers broadly to dried cannabis dispensed or otherwise obtained and used either for supervised medical purposes or for self-medication. In a more accurate context, the term “cannabis” or “dried cannabis” is preferred when describing the plant form.
The terms “cannabis” or “dried cannabis” refer to the marijuana in its plant form.
The term “pharmaceutical cannabinoid” refers to cannabinoids that may be available without a prescription that are generally 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 is cannabidiol if it is 100% pure and manufactured from cannabis stems or seeds, not leaves or flowers. Louisiama has now legalized other cannabinoids including THC, likely in the forms of capsules and tinctures only, expected to become available in the fall of 2018.
Tinctures are produced by steeping cannabis flowers in alcohol while applying low heat which allows the active compounds in cannabis to infuse into the alcohol. This infusion is then concentrated, resulting is a potent liquid that contains various cannabinoids and other constituents. Manufacturers often add carrier oils and other complementary ingredients, such as an orange oil to improve the taste of a tincture. Tinctures can be taken orally or sublingually (under the tongue).
Over-the-Counter Cannabinoid Medications:
Prescription Cannabis-Based Medications:
Clinical Applications of Cannabis:
Cannabis – Anxiety (coming soon)
Cannabis – Headaches (coming soon)
Cannabis – Inflammatory Bowel Disease (coming soon)
Cannabis – Neuroinflammation (coming soon)
Cannabis – Pain (coming soon)
Cannabis – Sleep (coming soon)
The Medical Science of Cannabis:
Cannabinoids and Terpenes:
Cannabinoids & Terpenes – An Overview (coming soon)
Terpenes – An Overview (coming soon)
Key to Links:
Grey text – handout
Red text – another page on this website
Blue text – Journal publication
This section remains incomplete and is still being edited for accuracy and completeness.
FDA-Approved Prescription Cannabinoids
The clinical benefits from marijuana are derived from the many constituents found in the plant, including more than 80 pharmacologically active cannabinoids. The two best understood and most common of these cannabinoids are THC (tetrahydrocannabinol) and CBD (cannabidiol). There is very limited scientific information on the pharmacology and toxicology of the other cannabinoids and pharmacologially active constituents found in cannabis.
With respect to the management of pain, studies suggest that THC alone may not be sufficient for a good analgesic effect. This means that THC may need to be combined with CBD in order to achieve good results.
THC has analgesic, anti-spasmodic, anti-tremor, anti-inflammatory, appetite stimulant and anti-emetic properties, but also mind-altering effects (euphoria). THC and its active metabolite, 11-Hydroxy-THC. are responsible for the “high” associated with use of marijuana.
CBD has anti-inflammatory, anti-convulsant, anti-psychotic, anti-oxidant, neuroprotective and immunomodulatory effects but does not produce mind-altering effects like euphoria. CBD is also thought to support sleep and reduce nausea, particularly related to chemotherapy. CBD, in combination with THC, modulates some of the side effects of THC, including reducing THC-induced anxiety.
Prescription Cannabinoid Medications
1) Cesamet (nabilone)
Cesamet (nabilone) is a synthetic cannabinoid intended for oral use. It is different from, but structurally similar to THC and offers similar benefits and side effects. It is a Schedule II controlled substance.
Cesamet (nabilone) – FDA-Approved Indications
Cesamet capsules are indicated only for the treatment of the nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments. This restriction is required because a substantial proportion of patients treated with Cesamet can be expected to experience side effects similar to THC including altered mental state and the potential for abuse.
Cesamet (nabilone) Pharmacology
Oral Cesamet (nabilone) is completely absorbed from the gastrointestinal tract and peak blood levels are achieved in about 2 hours. The plasma half-life (T1/2) for nabilone is about 2 hours. Cesamet can be taken with food or on an empty stomach.
Dosage and Administration
The usual adult dosage is 1 or 2 mg 2 times a day. On the day of chemotherapy, the initial dose should be given 1 to 3 hours before the chemotherapeutic agent is administered. To minimize side effects, it is recommended that the lower starting dose be used and that the dose be increased as necessary. A dose of 1 or 2 mg the night before may be useful. The maximum recommended daily dose is 6 mg given in divided doses three times a day.
Adverse Side Effects
The most frequent side effects reported with nabilone are drowsiness, vertigo, dry mouth and euphoria. However, most of the side effects that occur with nabilone are of mild to moderate severity. Cesamet should be used with caution in elderly patients aged 65 and over because they are generally more sensitive to the psychoactive effects of Cesamet.
1) The effects of Cesamet may persist for a variable and unpredictable period of time following use. Adverse psychiatric reactions can persist for 48 to 72 hours after stopping use.
2) Patients taking Cesamet may experience changes in mood (e.g., euphoria, detachment, depression, anxiety, panic, paranoia), impairments in cognitive performance and memory, a decreased ability to control drives and impulses, and alterations in the experience of reality (e.g., distortions in the perception of objects and the sense of time, hallucinations).
3) Cesamet can cause rapid heart rate, palpitations and a drop in blood pressure when standing.
4) Because of individual variation in response and tolerance to the effects of Cesamet, patients should remain under supervision of a responsible adult especially during initial use of Cesamet and during dose adjustments.
5) Patients treated with Cesamet should be cautious regarding driving, operating dangerous machinery, or engaging in any hazardous activity due to the potential for impairment.
6) Patients who are pregnant or planning to become pregant should not take Cesamet (Pregnancy
7) Cesamet should not be taken with alcohol, sedatives, hypnotics, or other psychoactive substances because these substances can potentiate the central nervous system effects of nabilone.
8) The safety aspects of the effects of liver and kidney impairment have not been well defined.
9) Cesamet should be used with caution in patients with a history of substance abuse, including alcohol or marijuana abuse or dependence, since Cesamet contains a similar active compound to marijuana.
10) Nabilone is highly bound to plasma proteins and therefore might displace other protein-bound drugs. Therefore, patients should monitor themselves for changes in effects and dosage need when taking other highly protein-bound drugs.
11) Cesamet undergoes extensive first pass hepatic metabolism which may lead to drug-drug interactions affecting the pharmacokinetics of co-administered drugs or of Cesamet itself.
12) The effects of QT prolongation potential by Cesamet have not been determined.
13) Data on the chronic use of Cesamet are not available; experience with cannabis suggests that chronic use of cannabinoids may be associated with reduced motivation, impaired cognition, memory and judgment.
14) Inhibition studies show that nabilone does not significantly inhibit the liver enzymes CYP1A2, 2A6, 2C19, 2D6, or 3A4. Nabilone does have a a weak inhibitory effect on CYP 2E1 and 3A4 but has a moderate inhibitory effect on CYP2C8 and 2C9. However, in clinical use, the very low nabilone blood concentration is unlikely to have significant clinical impact due to this inhibition.
15) Following oral administration, about 60% of nabilone and its metabolites are recovered in the feces and about 24% in urine. Therefore, it appears that the major excretory pathway is the biliary system.
16) Dogs have an unusual toxic vulnerability to Cesamet that is not understood; it is believed that dogs differs markedly from other species in its metabolism of Cesamet. Keep Cesamet away from dogs.
2) Epidiolex® (cannabidiol)
Epidiolex (cannabidiol) is an oral solution of cannabidiol (CBD) and is the first prescription, plant-derived cannabinoid medicine in the United States and the first in the new class of cannabinoid anti-epileptic medications.
Epidioles (cannabidiol) – FDA-Approved Indications
Epidiolex is FDA-approved only for the treatment of seizures associated with the specific pediatric seizure disorders, Lennox-Gastaut syndrome (LGS) and Dravet syndrome in patients two years of age or older, (pending DEA rescheduling).
3) Marinol® (dronabinol) – Synthetic THC
Marinol® (dronabinol), is synthetic THC supplied in capsules for oral use and is supplied as round, soft gelatin capsules containing either 2.5 mg, 5 mg, or 10 mg dronabinol.
Marinol® (dronabinol) – FDA-Approved Indications:
1) Anorexia associated with weight loss in patients with AIDS
2) Nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments.
Marinol® (dronabinol) – Clinical Pharmacology
After oral use, dronabinol has an onset of action of approximately 0.5 to 1 hour and a peak effect at 2 to 4 hours. Duration of action for psychoactive effects is 4 to 6 hours, but the appetite stimulant effect of dronabinol may continue for 24 hours or longer after administration. Due to the combined effects of extensive first pass hepatic metabolism and high lipid solubility, only 10 to 20% of the administered dose reaches the systemic circulation including both active and inactive metabolites.
Dronabinol stimulates sympathomimetic activity that may result in rapid heart rate and/or conjunctival injection (redness in eyes). Its effects on blood pressure are inconsistent, but some people experience a drop in blood pressure and/or syncope upon abrupt standing. Dronabinol also may have reversible effects on appetite, mood, cognition, memory, and perception. These phenomena appear to be dose-related, increasing in frequency with higher dosages, and subject to great interpatient variability.
Tolerance develop to many of the pharmacologic effects of dronabinol and other cannabinoids with chronic use including the cardiovascular and subjective adverse nervous system side effects. Tolerance does not appear to develop to the appetite stimulating effect associated with treating AIDS-related anorexia.
The pharmacologic effects of Marinol are dose-related and subject to considerable interpatient variability. Therefore, dosage individualization is critical in achieving the maximum benefit of Marinol Capsules treatment.
In the clinical trials, the majority of patients were treated with 5 mg/day Marinol, although the dosages ranged from 2.5 to 20 mg/day.
For an adult:
Begin with 2.5 mg before lunch and 2.5 mg before supper. If CNS symptoms (feeling high, dizziness, confusion, somnolence) do occur, they usually resolve in 1 to 3 days with continued dosage. If CNS symptoms are severe or persistent, reduce the dose to 2.5 mg before supper. If symptoms continue to be a problem, taking the single dose in the evening or at bedtime may reduce their severity.
When adverse effects are absent or minimal and further therapeutic effect is desired, increase the dose to 2.5 mg before lunch and 5 mg before supper or 5 and 5 mg. Although most patients respond to 2.5 mg twice daily, 10 mg twice daily has been tolerated in about half of the patients in appetite stimulation studies.
Antiemetic for Chemotherapy:
Most patients respond to 5 mg three or four times daily. Dosage may be escalated during a chemotherapy cycle or at subsequent cycles, based upon initial results. Therapy should be initiated at the lowest recommended dosage and titrated to clinical response. Administration of Marinol with phenothiazines, such as prochlorperazine (phenergan), may improved effectiveness as compared to either drug alone, without additional toxicity.
1) Seizure and seizure-like activity have been reported, Marinol should be used with caution in patients with a history of seizure disorder.
2) See Marijuana (Cannabis) Overview for additional warnings and precautions
4) Sativex® (nabiximols)
Sativex® is a prescription cannabis-based drug that is approved in Canada for the treatment of neuropathic pain associated with multiple sclerosis, and in three European countries for a number of other indications. Sativex® contains two standardized cannabis extract preparations, Tetranabinex®, which is high in THC, and Nabidiolex®, which is high in CBD. Sativex® contains equal proportions of Tetranabinex® and Nabidiolex®, and, hence, almost equal amounts of THC and CBD. THC and CBD represent approximately 70% of the product, with 5% of other cannabinoids, the remainder being terpenoids, flavonoids, sterols, alkanes, and other chemicals.
Sativex® is an oromucosal spray formulated to be absorbed from oromucosal surfaces: the buccal (cheek) or sublingual (under the tongue) surfaces. Absorption from these surfaces allows for direct access to the blood, avoiding the significant loss of bioavailability associated with oral ingestion and the breakdown of cannabis/cannabinoids by the stomach and liver.
Clinical Applications for Sativex®
Many clinical trials have demonstrated the safety and effectiveness of Sativex® in central and peripheral neuropathic (nerve) pain, rheumatoid arthritis and cancer pain. The recommended daily dose of Sativex® for the treatment of pain is a maximum of 32.4 mg THC and 30 mg CBD. The degree to which cannabinoid analgesics and the different ratios of the THC/CBD combination will be adopted in pain management remains to be determined.
Side Effects of Sativex®
Common side effects include dizziness, dry mouth, nausea, fatigue, somnolence, euphoria and vomiting.
Cannabinoid Drug Interactions
Cannabinoids and Opioids
There appears to be a synergistic analgesic (pain-relieving) benefit when cannabinoids are added to opioid treatment for 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.
Interestingly, 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 cannabinoids due to the very low density of cannabinoid (CB) receptors in brainstem cardiorespiratory centers. There does not appear to be any significant interactions with opioids regarding a cannabinoid effect on the metabolism of most opioids. However, there is research showing that CBD may inhibit CYP2D6, one of the liver enzymes responsible for metabolizing tramadol and codeine. Because the analgesic benefits from tramadol and codeine come from their active metabolites resulting from CYP2D6 metabolism, these two opioids may be less effective if taken with CBD.
Alcohol and Benzodiazepines
he 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, can partially antagonize the effects of THC.
Anticholinergic drugs (Tricyclic antidepressants (TCAs) and some muscle relaxers)
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.
National Academy of Sciences
This website appears to be good resource for exploring medical marijuana.
- Sativex Oromucosal Spray – Summary of Product Characteristics (SmPC) – (eMC)
- Cannabis-based medicines–GW pharmaceuticals: high CBD, high THC, medicinal cannabis–GW pharmaceuticals, THC:CBD. – PubMed – NCBI
- Delta-9-tetrahydrocannabinol and cannabidiol – Separating the chemicals from the “weed,” a pharmacodynamic discussion – 2016
- Delta-9-Tetrahydrocannabinol:Cannabidiol Oromucosal Spray (Sativex®): A Review in Multiple Sclerosis-Related Spasticity. – PubMed – NCBI
- Pharmacotherapeutic considerations for use of cannabinoids to relieve pain in patients with malignant diseases – 2018
Medical Marijuana – Prescribing Guidelines
- Simplified guideline for prescribing medical cannabinoids in primary care – Canadian Family Physician – 2018
- Physician Recommendation of Medical Cannabis Guidelines Calif Medical Assoc – 2011
- Prescribing smoked cannabis for chronic noncancer pain. Preliminary recommendations – Canadian Family Physician – 2014
Medical Marijuana – Opioids
- It is premature to expand access to medicinal cannabis in hopes of solving the US opioid crisis – 2018
- 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
- Patterns and correlates of medical cannabis use for pain among patients prescribed long-term opioid therapy. – PubMed – NCBI
- Associations between medical cannabis and prescription opioid use in chronic pain patients –
A preliminary cohort study – 2017
- The prevalence and significance of cannabis use in patients prescribed chronic opioid therapy: a review of the extant literature. – PubMed – NCBI
- The use of cannabis in response to the opioid crisis: A review of the literature. – PubMed – NCBI
- Medical Cannabis Laws and Opioid Analgesic Overdose Mortality in the United States, 1999–2010 – 2014
- Rationale for cannabis-based interventions in the opioid overdose crisis – 2017
- Cannabis and the Opioid Crisis – 2018
- Impact of co-administration of oxycodone and smoked cannabis on analgesia and abuse liability. – PubMed – NCBI
- Cannabinoid–Opioid Interaction in Chronic Pain
- Synergistic interactions between cannabinoid and opioid analgesics. – PubMed – NCBI
- FDA approves CBD drug – Epidiolex – The Washington Post
Medical Marijuana –Misc
- A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol and cannabidiol. – PubMed – NCBI
- Cannabis and cannabis extracts – greater than the sum of their parts? – 2001
- Medical cannabis and mental health: A guided systematic review. 2016 – PubMed – NCBI
- Epidemiological characteristics, safety and efficacy of medical cannabis in the elderly. – PubMed – NCBI
- Cannabis-conclusions – 2017 National Academy of Sciences
- Cannabis-chapter-highlights – 2017 National Academy of Sciences
- Cannabis-report-highlights – 2017 National Academy of Sciences
- 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
- Marijuana use and the risk of lung and upper aerodigestive tract cancers: results of a population-based case-control study. – PubMed – NCBI
- Cannabis use and cognitive function: 8-year trajectory in a young adult cohort. – PubMed – NCBI
- Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. – PubMed – NCBI
- Cannabinoids and Cytochrome P450 Interactions. – PubMed – NCBI Pharmacogenetics of Cannabinoids – 2018
- Systematic review of systematic reviews for medical cannabinoids – 2018
- Adverse effects of medical cannabinoids – a systematic review – 2008
- Cannabimimetic effects modulated by cholinergic compounds. – PubMed – NCBI
- Antagonism of marihuana effects by indomethacin in humans. – PubMed – NCBI
- Pharmacokinetics and pharmacodynamics of cannabinoids. – PubMed – NCBI
- Clinical Pharmacodynamics of Cannabinoids – 2004
- Affinity and Efficacy Studies of Tetrahydrocannabinolic Acid A at Cannabinoid Receptor Types One and Two. – 2017
Quality Control of Traditional Cannabis Tinctures – Pattern, Markers, and Stability – 2016
- Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review. – PubMed – NCBI
- Pharmacology of Cannabinoids
- Therapeutic potential of medicinal marijuana – an educational primer for health care professionals – 2018
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.
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