This section is a guide to safely starting marijuana and related products that impact the Endocannabinoid System (ECS). The ECS is a naturally occurring network in the body, especially the brain and nervous system. This section focused on managing chronic pain but the ECS regulates many physiologic functions including pain, inflammation, memory, mood, immunity, gastrointestinal (GI) function, appetite and metabolism.
For those interested in pursuing a trial of therapy with cannabis-based products, first read:
- Marijuana Use Introduction
- Potential for Harm
- Side Effects and Drug Interactions
- Cannabinoids and Opioids
LA Marijuana Products:
- LA Marijuana Products: Introductory Principles
- LA Marijuana Products: Tinctures
- LA Marijuana Products: Vape Cartridges & Vaporizers
- LA Marijuana Products: Ilera Vape Formulations
- LA Marijuana Products: RSO Formulations
- LA Marijuana Products: Plant Flower/Bud Products
- LA Marijuana Products: Edible Products
- LA Marijuana Products: Topical Products
Use and Dosing
- Marijuana (Cannabis) – Inhalation: Smoking vs Vaping
- Marijuana (Cannabis) – Oral Use (Edibles)
- Marijuana *Cannabis) – Topicals
- Marijuana (Cannabis) – Dosing
- Marijuana (Cannabis) – Dosing: Flower vs Pharmaceutical Products
- Cannabidiol (CBD) – Dosing, Products and Formulations
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.
Key to Links:
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Red text – another page on this website
Blue text – Journal publication
Marijuana (Cannabis)-based Medications for Pain
The recent introduction of marijuana-based products for medical use has coincided with two important developments in the understanding of chronic pain.
First, the understanding of the role of neuroinflammation (inflammation within the nervous system), along with the role of oxidative stress in the development and maintenance of chronic pain. Most chronic pain is believed to be the consequence of neuroinflammation within the peripheral and central nervous system including the spinal cord and brain. It is this neuroinflammation and oxidative stress that is the target of cannabis-based compounds as well as some other agents including palmitoylethanolamide (PEA), another new “tool in the toolbox.”
In addition, the neuroinflammatory process also plays a role in the way that opioids impact pain including the development of tolerance over time to analgesic benefits of opioids. Research suggests cannabis-based agents as well as PEA may reduce opioid tolerance and improve the analgesic benefits of opioids by reducing neuroinflammation and by other mechanisms as well. One argument for introducing cannabis-based products for the management of pain is to allow for the possible reduction or avoidance of opioids for pain.
Second, the recent discovery of the Endocannabinoid System (ECS) in mammals that is responsible for the therapeutic effects of marijuana, including its role in chronic pain. The primary mechanisms by which marijuana and its constituents engage pain and other benefits are through their interactions with ECS receptors and ECS compounds called “endocannabinoids.” Endocannabinoids are the natural marijuana-like compounds manufactured by the body that have important roles in pain and inflammation.
The Experience of Pain – a complex interplay that includes, mood, memory and emotion
A critical piece of the puzzle of how cannabis improves pain, particularly chronic pain, is understanding that the experience of pain is a complex interplay that includes mood, memory, emotion and other cognitive aspects in addition to simply the pain signals arising from injured tissues and related pain signaling in the peripheral and central nervous system. Because the endocannabinoid system is intimately involved the cognitive components of the pain experience, cannabinoids including THC and CBD significantly impact the experience of pain. As such, the benefits of cannabis products are more often associated with a patient’s improved ability to cope with their pain than any actual reduction in the severity of their pain per se.
Cannabis has also been found to be effective for anxiety, sleep and muscle spasm. Because there are many therapeutically active constituents in cannabis that contribute to these different benefits, the selection of products and/or formulations should also take into account these other treatment goals in addition to pain relief.
In addition to THC and CBD, terpenes are another group of compounds found in marijuana that are very important contributors to the therapeutic effects of cannabis. In particular, the terpene β-caryophyllene (BCP) is especially important in treating pain and inflammation and should be included with CBD along with other terpenes directed at pain, anxiety, and/or sleep.
The insights gained in these two arenas are the basis of the following recommendations for getting started with these new “tools in the toolbox” of chronic pain management.
It is recommended to begin with the safest agents – those with the least potential for side effects – as well as the least expensive and easiest accessible.
1. Start with Topical Cannabidiol (CBD) with Terpenes
First, begin with a trial of Topical CBD with β-caryophyllene (BCP)
A topical formulation is the least expensive starting point and the safest with only rare side effects outside of the rare allergic reaction. There is good evidence that CBD and β-caryophyllene (BCP) are effective for joint pain, muscle pain and peripheral neuropathy pain. While there may be other products of equivalent effectiveness available, currently the best recommendation is for a topical with high concentrations of CBD and BCP along with myrcene: CBD Body Cream with BCP by BioEntourage. It is currently available for $36/2 oz jar with discount code. To trial this for effectiveness, start with a generous application of the cream 3-4x/day for 3 days to establish maximum benefit, than cut back as desired.
If this product is effective, it establishes the fact that either CBD, BCP or their combination works! While a topical application only reaches cannabinoid receptors in the skin and superficial tissues, these compounds are likely to provide even more benefit if taken orally where they can enter the blood stream and access the same receptors present in deeper tissues and the nervous system where the most important pain processing occurs.
2. Next, add oral liquid CBD with BCP and other terpenes.
When you establish benefit with your optimal pattern of use of the topical cream, add a highly concentrated oral liquid formulation with CBD, BCP and terpenes while continuing to use the topical product. Start with a CBD dose of 10 mg, up to 25-50 mg/day, at night or split in two daily doses, 12 hours apart. This dosage range should meet most people’s need for pain and inflammation. Some people with rheumatoid arthritis or severe anxiety or insomnia may need higher doses.
While there may be other products of equivalent effectiveness available, currently the best recommendation is a liquid formulation with high concentrations of CBD, BCP and myrcene along with multiple other terpenes is: CarolinaCannabinoids’ CBD products. The 6000 mg CBD/30 ml bottles offer the most economical purchase while also providing water soluble, self micro emulsifying formulations that provide enhanced absorption and greater bioavailability than most other CBD products. These products do have very small amounts of THC (<0.3%), not enough to cause side effects, but enough to trigger a positive drug screen for marijuana. These products should be avoided by those with safety sensitive employment or those who are subject to drug screens at work.
1. If the addition of the oral liquid formulation of CBD provides no further benefit over the use of the topical, discontinue the oral formulation and maintain use of the topical formulation only.
2. If the addition of the oral liquid formulation of CBD is more effective than the topical alone, discontinue the topical to determine if the oral formulation by itself is better than the combination of the topical and oral formulations. If discontinuing the topical results in diminished benefit, then one nay need to use both the topical and oral formulation to achieve maximum benefit.
3. Add Palmitoylethanolamide (PEA)
Palmitoylethanolamide, or PEA, is a natural food-based supplement that has extensive research demonstrating its effectiveness for nerve pain and inflammation, and especially neuroinflammation. In fact, the clinical evidence for PEA in human studies of pain is better than that for CBD. It has no side effects and is less expensive than CBD.
PEA has multiple mechanisms implicated in how it works but one important mechanism involves the endocannabinoid system (ECS) where PEA works synergistically with CBD and BCP. For example, BCP induces the ECS to manufacture endocannabinoids that relieve pain and PEA inhibits the enzyme that breaks down the endocannabinoids so they last longer and maintain greater pain benefit.
Oral PEA vs Topical PEA
PEA can be taken orally or applied topically. For those with peripheral neuropathy (PN), it is advised to start the PEA trial with topical PEA to areas affected by PN. Next, add oral PEA to determine if oral PEA plus topical PEA is more effective than the topical PEA alone. As above with CBD, one must determine the relative benefits of topical vs oral vs the combination of both formulations of PEA to conclude which provides the best, most cost-effective benefit.
The topical PEA should be applied 3-4x/day initially to assess benefit, then adjust the dose as needed. The usual oral dose for PEA is 600 mg twice a day. It may take 2-4 weeks for the benefits of PEA to manifest.
4. Add Tetrahydrocannabinol (THC) to CBD, Terpenes and PEA
When, despite the use of CBD products with appropriate terpene and PEA profiles and doses still do not meet one’s desired cannabis-based therapeutic goals, then adding THC to the mix is the next step. In Louisiana, adding THC requires a prescription/”recommendation” from a physician licensed to prescribe THC-based products. Chronic pain associated with a failed response to conservative, conventional treatment is legally eligible for management with THC products, but this should be evaluated by a physician.
Currently available THC-based products have different strengths and combinations of THC, CBD and terpenes. Selecting the most appropriate THC product and dose should be based on evaluation by your physician. However, certain considerations for adding THC include:
Start low, Go slow
Because THC is responsible for most of the side effects associated with the use of marijuana-base products, the inexperienced user should start with low doses of a THC tincture, 2-5 mg at first, using one to five drops at a time. Slowly increase the dosage by adding more drops after you see how you feel. Wait 15 minutes to determine the effects and if needed, slowly increase the dosage by adding another drop and waiting an additional 15 minutes. Repeat this process until you determine how much is enough to relieve your symptoms. As one becomes familiar with the effects of THC, doses can be slowly increased based on effectiveness and tolerability, but the inexperienced user will not likely need to exceed 10 mg per dose initially. THC dosing should be guided by its purported benefits. In addition to its benefits for pain, THC also promotes relaxation, appetite, pleasure, euphoria, and it may reduce depression.
The therapeutic benefits of THC and CBD may be influenced by the ratio of these two cannabinoids. For pain benefits, it is probably best to start with a balanced formulation with equal amounts of THC and CBD. For anxiety and sleep benefits, higher doses of CBD compared with THC may be advisable. It has been reported that lower CBD doses may be stimulating and energizing whereas higher CBD doses become sedating, but these effects are individually determined. Lower THC:CBD ratios are purported to have less THC-based side effects, including increased appetite, anxiety, impaired thinking and the “high.” As a general rule, the THC:CBD ratio should be started low and increased as needed based on therapeutic benefits as well as side effects: a bit of trial and error is necessary.
Choice of Form
THC comes in liquid tinctures, edible forms, and inhalable forms for smoking or vaping, and topical forms, creams and balms. Topical forms are safest because they are unlikely to have side effects. But topicals offer no effects on anxiety, sleep, relaxation or appetite, so their clinical application is limited to localized relief of pain, inflammation, or skin conditions.
Tinctures are usually the preferred form to start medical marijuana when seeking additional benefits other than pain, especially in regards to determining an appropriate dosage. Tinctures are drops taken under the tongue that allows quicker absorption into the bloodstream. Their effects are felt within 5-15 minutes and can last for 30 minutes to 3 hours.
Edibles are the most psychoactive, intoxicating, and unpredictable method of using cannabis and may be subjectively different from inhalable use. It is very difficult to predict how one will react to an edible and how much will be too much. Start with a very small dose of edibles and wait for a full 1 to 2 hours to determine its effects before taking more. It is very easy to over-medicate with edibles because their effects may take up to several hours to begin working. Taking more edible before the first dose begins working can lead to unwanted side effects (drowsiness, anxiety, headaches). If one chooses ingested cannabis, capsules are the most reliable means to identify the correct dose to relieve your symptoms.
Choice of Formulation
THC products are available as isolates that have only THC in them, such as tinctures and edibles. Since THC is likely to work better when combined with CBD and appropriate terpene profiles based on the condition(s) treated, THC isolates may be the best choice, therapeutically and financially, as long as they are taken with appropriate CBD/terpene products. On the other hand, THC products, especially flowers, that have their own terpene profiles may have the advantage of supplementing additional terpenes for their specific therapeutic benefits, even when combined with a CBD/terpene product.
When selecting a cannabis strain, there are 3 categories of strain – Indica, Sativa, or Hybrid. Indica strains tend to be relaxing and best for evening or sleep. Sativa strains tend to be energizing and uplifting and usually best for daytime use. Hybrid strains can be indica-dominant or sativa-dominant. Indica-dominant hybrids are likely to be relaxing but not too sedating. Sativa-dominant hybrids are likely to be energizing with some relaxation. This commonly promoted description of strain properties may serve as a starting point but unfortunately it is generally over-simplified and inaccurate due to massive interbreeding of strains over recent years. Of note, none of the cannabis flowers offered by the LA-based dispensary pharmacies have any CBD in them. See:Selecting Flower Products
5. Add Alternative Agents to Facilitate Pain Management
Finally, if the combination of THC, CBD, terpenes and PEA do not achieve ones therapeutic goals, the next step is to add other nutriceutical supplements that may work synergistically with these compounds and the endocannabinoid system. These other agents include NRF2 activators and anti-inflammatories such as curcumin, Resveratrol and quercetin.
National Academy of Sciences
These lay-person websites appear to be good resources for exploring medical marijuana:
Medical Marijuana – Federal Law
Medical Marijuana – Louisiana Law
- HOUSE BILL NO. 225 – 2017 Regular Session
- Louisiana medical marijuana expansion bill signed into law – May 20, 2016
- Now in Effect, Louisiana Medical Marijuana Law Shields Patients and Caregivers from Prosecution – Aug 5, 2016
Cannabidiol (CBD)- Overviews
- CANNABIDIOL (CBD) Pre-Review Report WHO 2017
- Cannabidiol – State of the art and new challenges for therapeutic applications. – 2017 PubMed – NCBI
CBD – Anxiety
- Overlapping Mechanisms of Stress-Induced Relapse to Opioid Use Disorder and Chronic Pain – Clinical Implications – 2016
- Cannabidiol Modulates Fear Memory Formation Through Interactions with Serotonergic Transmission in the Mesolimbic System – 2016
- Cannabidiol regulation of emotion and emotional memory processing: relevance for treating anxiety-related and substance abuse disorders. – PubMed – NCBI
- Review of the neurological benefits of phytocannabinoids – 2018
- Plastic and Neuroprotective Mechanisms Involved in the Therapeutic Effects of Cannabidiol in Psychiatric Disorders – 2017
- Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report. – PubMed – NCBI
- Evidences for the Anti-panic Actions of Cannabidiol – 2017
- Cannabidiol, a Cannabis sativa constituent, as an anxiolytic drug – 2012
- Cannabidiol Reduces the Anxiety Induced by Simulated Public Speaking in Treatment-Naïve Social Phobia Patients – 2011
CBD – Interaction with THC
- Cannabidiol: a promising drug for neurodegenerative disorders? – PubMed – NCBI
- Oral Cannabidiol does not Alter the Subjective, Reinforcing or Cardiovascular Effects of Smoked Cannabis – 2015
- Taming THC – potential cannabis synergy and phytocannabinoid-terpenoid entourage effects – 2011
- A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol and cannabidiol. – PubMed – NCBI
CBD – Metabolites
- Human Metabolites of Cannabidiol – A Review on Their Formation, Biological Activity, and Relevance in Therapy – 2016
CBD – Drug-Metabolic Interactions
- Cannabidiol, a Major Phytocannabinoid, As a Potent Atypical Inhibitor for CYP2D6 – 2011
- The Effect of CYP2D6 Drug-Drug Interactions on Hydrocodone Effectiveness – 2014
- Characterization of P-glycoprotein Inhibition by Major Cannabinoids from Marijuana – 2006
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
- A cannabis oracle? Delphi method not a substitute for randomized controlled trials of cannabinoids as therapeutics – 2021
- Consensus recommendations on dosing and administration of medical cannabis to treat chronic pain – results of a modified Delphi process – 2021
- Consensus‐based recommendations for titrating cannabinoids and tapering opioids for chronic pain control – 2021
- Clinicians’ Guide to Cannabidiol and Hemp Oils – 2019
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, Chronic Pain – Cannabinoids & Palmitoylethanolamide
- Therapeutic utility of palmitoylethanolamide in the treatment of neuropathic pain associated with various pathological conditions – a case series – 2012
- Palmitoylethanolamide, a naturally occurring lipid, is an orally effective intestinal anti-inflammatory agent – 2013
- Cannabinoid-based drugs targeting CB1 and TRPV1, the sympathetic nervous system, and arthritis – 2015
- Fatty acid amide hydrolase: biochemistry, pharmacology, and therapeutic possibilities for an enzyme hydrolyzing anandamide, 2-arachidonoylglycerol,… – PubMed – NCBI 2001
- Endocannabinoid-related compounds in gastrointestinal diseases – 2018
- ‘Entourage’ effects of N-palmitoylethanolamide and N-oleoylethanolamide on vasorelaxation to anandamide occur through TRPV1 receptors – 2008
- Medical Cannabis and Cannabinoids- An Option for the Treatment of Inflammatory Bowel Disease and Ca
ncer of the Colon? – 2018
- Effects of homologues and analogues of palmitoylethanolamide upon the inactivation of the endocannabinoid anandamide – 2001
- Phytocannabinoids beyond the Cannabis plant – do they exist? – 2010
- Palmitoylethanolamide, endocannabinoids and related cannabimimetic compounds in protection against tissue inflammation and pain: potential use in c… – PubMed – NCBI
- Cannabinoids as pharmacotherapies for neuropathic pain – from the bench to the bedside. – 2009
- Correction – Effect of a new formulation of micronized and ultramicronized N-palmitoylethanolamine in a tibia fracture mouse model of complex regional pain syndrome – 2018
- Palmitoylethanolamide induces microglia changes associated with increased migration and phagocytic activity – involvement of the CB2 receptor – 2017
- Mast cells, glia and neuroinflammation – partners in crime? – 2013
- A Pharmacological Rationale to Reduce the Incidence of Opioid Induced Tolerance and Hyperalgesia – A Review – 2018
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 Te
trahydrocannabinolic 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
- Medical Marijuana for Treatment of Chronic Pain and Other Medical and Psychiatric Problems – A Clinical Review – 2015
Medical Marijuana – Product Evaluation
- The Cannabinoid Content of Legal Cannabis in Washington State Varies Systematically Across Testing Facilities and Popular Consumer Products – 2018
- Quality Control of Traditional Cannabis Tinctures – Pattern, Markers, and Stability – 2016
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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