#81 - Debra Kimless, M.D. & Steve Goldner, J.D.: Cannabis – the latest science on CBD & THC
Dr. Debra Kimless (CMO) and Steve Goldner (CEO, Pure Green) explore medicinal cannabis, differentiating THC, CBD, and hemp. They discuss cannabinoid mechanisms, benefits, vaping risks, and their mission to deschedule cannabis for medical access.
Deep Dive Analysis
17 Topic Outline
Guests' Background and Interest in Medical Cannabis
Historical Use and Legal Scheduling of Cannabis
THC: Mechanism of Action and Intoxicating Effects
CBD: Distinction from THC and Therapeutic Mechanisms
Hemp: Legal Definition, Industrial Uses, and Farm Bill
CBD's Legal Status and Clinical Trial Results
Safety Profile and Toxicity of THC
Marijuana as a Gateway Drug: Evidence and Arguments
Routes of Administration: Smoking, Vaping, and Edibles
Vaping-Related Acute Respiratory Illnesses
THC Tolerance and Therapeutic Index
Consumer Demand for Cannabis: Medical vs. Recreational
Synthetic Cannabinoids and Plant-Derived Compounds
CBD for Sleep: Efficacy and Mechanism
Pure Green's Business Model and Research Funding
Managing Hype and Misinformation in Cannabis Treatment
Future of Cannabis: Legalization and Research Challenges
8 Key Concepts
CB1 and CB2 Receptors
These are docking stations in the brain and peripheral nervous system that cannabinoids like THC activate. CB1 receptors are predominantly found in the brain and peripheral nervous system, while CB2 receptors are mainly located on immune cells peripherally.
Endocannabinoid System
This is the body's naturally occurring system of neurotransmitters and receptors that interacts with cannabinoids. CBD works by indirectly activating this system or by acting on entirely different receptors, contributing to its therapeutic effects without intoxication.
Hemp (Legal Definition)
Legally, hemp is defined as a cannabis cultivar that contains less than 0.3% by weight of THC or THCA, distinguishing it from marijuana which has higher THC concentrations. This legal distinction was formalized by the Farm Bill, allowing for its cultivation and processing.
Decarboxylation
This is a chemical process that requires applying time and temperature to the acid forms of cannabinoids (e.g., THCA, CBDA) to convert them into their active, non-acid forms (THC, CBD). This conversion is necessary for the intoxicating effects of THC and for the full therapeutic potential of many cannabinoids.
Therapeutic Index (Therapeutic Window)
This metric represents the ratio between the lethal dose 50 (LD50) and the effective dose of a drug. For cannabis, the therapeutic index is extremely wide, estimated at 1:20,000 to 1:40,000, indicating a very high safety profile and making it difficult to overdose fatally.
Hyperalgesia
This is a paradoxical phenomenon observed with prolonged opiate use where, instead of continued pain relief, patients experience an enhancement or increase in pain. This effect is not seen with THC, which does not lead to the same kind of tolerance or pain sensitization.
Entourage Effect
This concept describes the synergistic interaction between various compounds found in the cannabis plant, including cannabinoids, terpenes, and flavonoids. It suggests that these compounds work together to produce a greater therapeutic effect than any single compound in isolation.
Investigational New Drug (IND) Exemption
An IND is an exemption from federal law that allows a pharmaceutical company to ship an unapproved drug across state lines for the purpose of conducting clinical trials. It is a critical step in the drug development process, allowing for the collection of safety and efficacy data under FDA oversight.
10 Questions Answered
Historically, cannabis has been used as a medicine for over 5,000 years, with applications ranging from pain relief to memory support in ancient cultures.
THC directly binds to CB1 and CB2 receptors, leading to intoxicating effects and other physiological changes, while CBD works indirectly by interacting with the breakdown products of natural endocannabinoids or by acting on entirely different receptors, thus not causing intoxication.
Hemp is legally defined as a cannabis cultivar containing less than 0.3% by weight of THC or THCA, distinguishing it from marijuana which has higher THC concentrations.
While THC has a very low toxicity potential (no known lethal dose), sensitive individuals may experience anxiety, panic, or rapid heartbeat, and its effects can be influenced by set and setting.
No, NIDA (National Institute on Drug Abuse) no longer considers cannabis a gateway drug, and some studies suggest it may even serve as an 'exit drug' to help people move off other addictive substances.
Smoking or vaping provides rapid onset of effects but shorter duration, with potential risks from combustion byproducts or unknown vape additives, while edibles have a delayed onset (60-90 minutes) but longer duration (8-10 hours) due to liver metabolism converting THC into a more intoxicating metabolite.
While THC can down-regulate receptors with over-consumption, these receptors can be reset quickly by stopping use for a couple of days, and studies suggest patients often stabilize at a consistent daily dose without needing increasing amounts.
Anecdotal evidence and pharmacovigilance data suggest CBD, particularly in water-soluble forms, can help people fall asleep quickly, experience a good night's sleep, and wake up refreshed without grogginess, likely due to its anti-inflammatory effects and GABA receptor activation.
Due to the federal illegality of cannabis, most universities and medical institutions are hesitant to conduct research on the plant or its compounds, fearing jeopardy to their federal funding, despite growing scientific interest.
Consumers should buy from legal dispensaries, ask for a certificate of analysis to verify product contents and safety, and ideally seek guidance from physicians knowledgeable in cannabinoid medicine.
17 Actionable Insights
1. Avoid Unregulated Cannabis Purchases
Do not buy cannabis products online or off the street, as there is no guarantee of testing, safety, or purity, similar to not taking candy from strangers.
2. Purchase from Legal Dispensaries
If you live in a legal state, become a certified patient, consult with a physician, and purchase cannabis products from a legal dispensary to ensure guidance and safety.
3. Request Cannabis Certificate of Analysis
When purchasing cannabis products, always ask for the Certificate of Analysis (COA) to verify testing for safety, potency, and the absence of adulterants.
4. Find Expert Cannabis Clinicians
Seek guidance from expert cannabinoid medicine physicians by consulting the Society of Cannabis Clinicians, which provides a list of doctors by state.
5. Beware Vaping Additives
Exercise caution with vape cartridges, as thinning agents like PG, PEG, or Vitamin E acetate, while generally safe for ingestion, can create harmful byproducts like formaldehyde when heated and inhaled.
6. Avoid Inhalational Cannabis Methods
Avoid inhalational methods of cannabis use, as consistent dosing is difficult to control, making it challenging for physicians to accurately titrate and manage patient treatment.
7. Consider Cannabinoid Microdosing
To achieve therapeutic effects without intoxication, consider microdosing cannabinoids by using very small amounts to activate cellular processes.
8. Leverage Cannabinoid Synergistic Effects
When choosing cannabinoid products, look for formulations that combine isolated cannabinoids with other constituents to capitalize on synergistic effects, potentially allowing for lower doses and fewer side effects.
9. Consider CBD for Improved Sleep
Consider using CBD, potentially in a water-soluble form for better efficacy, to help fall asleep quickly, achieve a good night’s sleep, and wake up refreshed without grogginess.
10. Edibles Metabolite More Intoxicating
Be aware that when ingested, THC is converted into a metabolite in the liver that is even more intoxicating than THC itself, which can lead to a more intense experience than inhalation.
11. Reset THC Tolerance with Pause
If you experience down-regulation of THC receptors from over-consumption, you can quickly reset your tolerance by stopping use for a couple of days.
12. Avoid Cannabis on Developing Brains
Do not use chemical substances like cannabis on a developing brain unless there is a clear medical necessity, due to potential unknown effects.
13. Raw Cannabis Not Intoxicating
Eating the raw cannabis plant will not produce intoxicating effects because its chemical constituents are not in an activated form; it may only cause a bellyache from fiber.
14. Consume Hemp Seeds for Nutrition
Incorporate hemp seeds into your diet as they offer an excellent omega-3 to omega-6 profile and are a wonderful source of protein.
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8 Key Quotes
My mom was dying from a complication from a pharmaceutical drug. And because of that, I started really thinking about what we learned in medical school, how we were trained, and what else could there have been for my mom as an option other than a pharmaceutical.
Debra Kimless
Developing methadone at the beginning of my career was a first bookend. And now developing all these formulations to help people with cannabis is the second bookend on my career.
Steve Goldner
I always say that cannabis is a gateway more towards health than to other drugs.
Debra Kimless
It's not just what the LD50 is, it's how far the LD50 is from the use dose.
Peter Attia
We call it a therapeutic window. I call that a therapeutic garage door.
Debra Kimless
The problem with opiates. Opiates sit on these, their own docking station, and they do down-regulate very quickly, which means that you require more and more for the same effect. And then it does something really strange. It flips. And after a certain amount of opiates, your pain gets enhanced, not decreased. And it's called hyperalgesia.
Debra Kimless
I'm kind of amazed, is there not a comparable group that is advocating for the judicious study of THC and CBD?
Peter Attia
This is a human rights issue. You hit the nail on the head. I mean, that's a huge problem for me as a physician to guide patients, which I do.
Debra Kimless