Evidence Mounts for Low and Ultra-Low Doses of Cannabinoid-Based Therapy 

MARCO ISLAND, Florida—Dustin Sulak, DO, an integrative medicine physician based in Falmouth, Maine, has been fascinated by cannabis since he was a teenager.

With 13 years of clinical experience in treating thousands of patients with cannabis, Dr. Sulak is an internationally recognized educator in the field of cannabinoid medicine. He is also the Chief Medical Officer of Healer, a company he co-founded in 2015, where he offers educational programs for clinicians and others in the cannabis industry, as well as complementary online educational programs geared toward patients.

Dr. Sulak spoke to AJEM at the CannMed 23 Innovation & Investment Summit in Marco Island, Florida, where he gave a presentation titled “Low and Ultra-Low Doses of Cannabinoids: Are We Missing the Sweet Spot?”

“It looks like there’s something very interesting happening in the low and ultra-low dose range that may have physiologic mechanisms of action that are distinct from what we’re seeing in the more moderate or high-dose range.” 

Dustin Sulak, DO

The Hormetic Principle

In his presentation, he explained the phenomenon known as hormesis, wherein most toxins, taken at a low enough dose, do not have a toxic effect overall but manage to upregulate some cell defense and repair mechanisms.

“Through this hormetic effect, you can use toxic compounds to get a net benefit for health and healing,” he said. “For example, take a very low dose of a toxin and gradually, over time, you might become resilient to accidental exposure to a high dose of that same toxin because you’ve upregulated the pathways you need to deal with that exposure.”

The best analogy, he said, is exercise.

“If you exercise too much, you’ll hurt yourself. But if you exercise the right amount, you’ll get stronger,” he said. He pointed out that the endocannabinoid system (ECS) responds to exercise, doubling anandamide concentrations after 30 minutes of running on a treadmill. He noted that the same is true for anandamide concentrations in singers after a 30 minute vocal session. “It’s something that’s healthy at a low dose but toxic at a high dose, so how do you get it right? How do you know?”

The Case for Low-Dose Cannabis Therapy 

Dr. Sulak said such paradoxical effects are seen throughout the ECS.

“The most obvious example is that a THC [delta-9-tetrahydrocannabinol] overdose is characterized by most of the symptoms that THC would correct at an appropriate dose,” he said. “We also see trends in cannabis in which as people increase their dose, they can get less benefit. But if they decrease their dose, they can get more benefit.”

He added, “It looks like there’s something very interesting happening in the low and ultra-low dose range that may have physiologic mechanisms of action that are distinct from what we’re seeing in the more moderate or high-dose range.” 

Dr. Sulak considers anything less than 0.5 mg per day to be an ultra-low dose of cannabinoids for an adult. In his practice, daily doses of total oral cannabinoids range from 0.01 to 100 mg/kg of body weight or 0.7 to 7000 mg daily for a 70-kg adult. Based on the evidence from the preclinical literature, he’s interested in treating patients with even lower doses to explore this ultra-low dose range. Through his company Healer, Dr. Sulak currently makes medical cannabis products in the Maine and Maryland marketplace, as well as hemp products that can be shipped across state lines.

Targeted Cannabinoid-Based Therapy

The cannabis plant contains at least 120 cannabinoids and possibly 5000 distinct phytochemical compounds. Evidence suggests that very low doses of a given trace constituent could be effective in certain diseases.

One possibility is Alzheimer’s disease, Dr. Sulak said. In a recent experiment, THC given at 3 mg/kg of body weight daily for an entire month reversed cognitive decline in elderly mice with dementia.¹

“Those old mice started acting like young mice on behavioral tests. When their brain volume increased, the brain actually started looking like the brains of young mice, and their gene expression resembled the gene expression of young mice,” Dr. Sulak said.

In a different study in a similar setting with even older mice, a single ultra-low dose of THC produced the same or even stronger results than one month of daily dosing in the aforementioned study in terms of reversing dementia-like symptoms—even 7 weeks later.²

Dr. Sulak’s conclusion: Cannabis may work wonders for those with Alzheimer’s disease.

“The most common reason it’s being used in that population right now is to treat the symptoms of agitation. Maybe the second most common would be pain or sleep disturbance. But a lot of people aren’t focusing on what cannabis can do for the primary pathophysiology of the condition. Could we improve cognition? Could we stop or slow down the decline? And might we be able to achieve these outcomes with much lower doses, as has been demonstrated in rodents? These are the important questions.”