Clinical Review: Kratom and Synthetic Cannabinoids Share Pattern of Escaping Regulation While Posing Opioid and Psychiatric Risks

Why it matters

Primary care physicians are increasingly seeing patients who use kratom and synthetic cannabinoids — two emerging substance categories that produce serious adverse effects and are consistently one step ahead of regulation. A peer-reviewed clinical review in a primary care journal helps frontline providers recognize risks, understand mechanisms, and guide management.

The big picture

Both kratom and synthetic cannabinoids (K2/Spice) exploit regulatory gaps: they are marketed as natural or legal alternatives, product formulations change faster than scheduling actions, and their adverse effects can be severe and underrecognized. The parallel regulatory history — including repeated attempts to schedule new analogs — reflects the same dynamic. This review situates kratom alongside K2 for a primary care audience at a moment when both are subject to new federal and state actions.

Key findings

• Kratom contains mitragynine and 7-hydroxymitragynine; it produces opioid and stimulant effects and carries risks of opioid toxicity, withdrawal, and product contamination.
• Synthetic cannabinoids are cannabinoid receptor agonists structurally unrelated to cannabis but with much higher receptor affinity; they are linked to elevated rates of psychosis, seizures, stroke, and myocardial infarction.
• Both substance classes exploit poor regulatory oversight; synthetic cannabinoid policy has had limited effectiveness because manufacturers continuously introduce new compounds that bypass existing schedules.
• Users of both kratom and synthetic cannabinoids often self-treat pre-existing mental health or pain conditions, complicating risk assessment.
• Withdrawal from high-dose kratom products requires the same clinical approach as opioid withdrawal, including buprenorphine/naloxone in some cases.
• Conventional urine drug screens often do not detect kratom alkaloids or novel synthetic cannabinoids, making clinical identification difficult.

What they say

The authors conclude that "both kratom and synthetic cannabinoids, often marketed as 'natural' or 'legal' alternatives, carry serious health risks including opioid toxicity, addiction, and dependent behaviors, aided by a persistent lack of effective regulation."

Bottom line

Primary care clinicians need to screen for kratom and synthetic cannabinoid use, as both substances produce serious opioid- or psychiatric-class adverse effects that standard drug panels frequently miss.