Buprenorphine and methadone are the classically accepted drugs for weaning addicts off opioids. Though less dangerous, they’re narcotics with the potential to be abused.
Even when addicts have everything going for them — a strong support group and access to buprenorphine or methadone — they relapse 90 percent of the time. “Opioid withdrawal may be the worst experience a human being can endure. It won’t kill you, but it feels like it will,” said Jay McLaughlin, Ph.D., an associate professor of pharmacodynamics.
In comes kratom, or Mitragyna speciosia, a tropical tree from southeast Asia. For generations, farmers there have chewed the leaves or ground them up to make a tea, giving them an extra mental and physical boost to continue working in the fields. In addition, it has been traditionally used as a substitute to avoid withdrawals when opium is not available.
More recently, researchers in the College of Pharmacy have studied its potential to wean addicts off heroin or prescription opioids. It activates the same opioid receptors and appears to satisfy the craving while lessening the risk of respiratory depression.
Respiratory depression is the most common cause of mortality when opioid users overdose. A normal breathing rate is 12–20 breaths per minute, but after an overdose, users can have their breathing slowed to one or two breaths per minute. A major goal of UF’s kratom initiative is to figure out whether kratom carries these risks.
Preclinical kratom research at UF begins with Christopher McCurdy, Ph.D., a professor of medicinal chemistry, who isolates compounds from crushed leaves in his laboratory. He passes the compounds onto Bonnie Avery, Ph.D., a clinical professor of pharmaceutics, who weighs and analyzes each compound to identify the component chemicals in each sample. She also evaluates the plant material in animals: how much is present in the body, where the compounds accumulate and how the body metabolizes and ultimately removes the compounds.
Lance McMahon, Ph.D., a professor and chair of the department of pharmacodynamics, takes the compound and tests the kratom chemicals in animal models. He and McLaughlin study the chemicals in combination with receptor blockers to help identify receptor sites of action.
McMahon’s and McLaughlin’s models explore whether kratom has the same behavioral effects as opioids, and what the effects are after chronic treatment. “We hypothesize the magnitude of kratom withdrawal is less than it is for many prescription opioids,” he said. “But the question remains, how much less?”
Just as marijuana contains cannabinoids recognized for their therapeutic benefit and tetrahydrocannabinol, or THC, known for its euphoric high, kratom too contains numerous compounds. Some are more therapeutic, others more euphoric.
McLaughlin researches kratom chemicals in mouse models to find out which have the greatest therapeutic benefit and which have the highest abuse risk.
From his models, mice do not develop tolerance to “7-OH mitragynine,” a chemical compound found in kratom, but they do experience conditioned place preference — meaning they will hang out in the test chamber where they previously received it, hoping for more. Another compound “mitragynine pseudoindoxyl” does not produce conditioned place preference, and although tolerance does develop, it does so far less than to clinical opioids like morphine.
“The hope is to find a pain killer without addiction and respiratory issues,” McLaughlin said. “I don’t think it’s a hope; I think it’s going to happen.” Kratom may fulfill this expectation.