Drug & supplement interaction

K2/spice + Primidone

Primidone brand name: Mysoline.

Moderate Interaction
Medically reviewed by · Updated September 2026
The bottom line Moderate

K2/spice has a moderate interaction with Primidone. Theoretically, K2/spice might increase or decrease the effectiveness of anticonvulsant drugs.

Read the full interaction report
SeverityModerate
LikelihoodPossible
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

K2/spice and Primidone

Here is the interaction we found between these two, with the evidence behind it.

Moderate

ANTICONVULSANTS

Why this applies to Primidone

Primidone falls under ANTICONVULSANTS — the group K2/spice interacts with.

Theoretically, K2/spice might increase or decrease the effectiveness of anticonvulsant drugs.
Some animal research suggests that certain types of synthetic cannabinoids found in some K2/spice products can potentiate the effects of anticonvulsants. However, seizures have also been reported with inhalation of K2/spice.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

First things first: K2/Spice isn't a real supplement. It's plant material sprayed with lab-made cannabinoid chemicals, and it's genuinely dangerous, linked to seizures, heart trouble, psychosis, and even deaths. That alone makes it a bad mix with a seizure medicine like primidone (Mysoline).

On paper, the picture cuts both ways. Some animal studies hint that synthetic cannabinoids could strengthen primidone's effect, which might mean more drowsiness, dizziness, unsteadiness, or feeling foggy. But K2/Spice has also triggered seizures on its own, which works directly against what primidone is trying to do, and could undo your seizure control. This is theory-level concern, not proven, but the unpredictability is the real worry. Please talk with your doctor or pharmacist before mixing anything with your seizure medicine.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Davidson C, Opacka-Juffry J, Arevalo-Martin A, Garcia-Ovejero D, Molina-Holgado E, Molina-Holgado F. Spicing up pharmacology: a review of synthetic cannabinoids from structure to adverse events. Adv Pharmacol 2017;80:135-68. PubMed
  2. Tait RJ, Caldicott D, Mountain D, Hill SL, Lenton S. A systematic review of adverse events arising from the use of synthetic cannabinoids and their associated treatment. Clin Toxicol (Phila) 2016;54(1):1-13. PubMed

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

K2/spice Also Interacts With Other Medications

K2/spice has 207 moderate known drug interactions in our database — the Primidone one above is one of them. If you take anything else, check it against the full list below.

Moderate 207 No known interaction 2,623 (incl. Primidone)
Taking anything else?

Check Another of Your Medications Against K2/spice

Covers the 2,830 medications we’ve checked against K2/spice. Pick one to open its full report.

From our Q&A

Questions About K2/spice or Primidone

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers K2/spice or Primidone, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Primidone

This page covers K2/spice only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Primidone page lists 124 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Beer (major), Gamma-hydroxybutyrate (ghb) (major) and Kava (major).

By severity: 7 major · 101 moderate · 16 minor.

Open the Primidone interaction page

How much people look this up

Where K2/spice and Primidone Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement K2/spice
Steady interest

#751 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Primidone
Top half

#772 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About K2/spice

What is K2/spice?

  • Recreational drug ('legal high')
  • Marijuana substitute
  • Mood or perception changes
  • Sometimes used to avoid drug testing

K2/Spice is NOT a herbal supplement — it is plant material sprayed with man-made synthetic cannabinoid chemicals. It is dangerous, unpredictable, and has caused seizures, heart problems, psychosis, and deaths, so it should not be used.

Read the full K2/spice monograph & all interactions
Medication

About Primidone

What Is Primidone Used For?

Brand name: Mysoline

Primidone is used to control several types of epileptic seizures, including grand mal (large, whole-body seizures), psychomotor seizures (seizures that affect movement and awareness), and focal seizures (seizures starting in one part of the brain). It can be used alone or alongside other anti-seizure medications.

Both Mysoline and primidone tablets may also help control grand mal seizures that have not responded to other anti-seizure treatments.

See full Primidone drug information
Keep checking

Other Drugs & K2/spice

Browse every other medication we’ve checked against K2/spice — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
207Moderate
0Minor
2,622No known interaction
207 Moderate 2,622 No interaction
Moderate

207 interactions

Showing 60 of 207 moderate interactions — see all 207 on the K2/spice page.

No interaction 2,622 drugs checked — show the list

We also checked K2/spice against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,622 medications checked with no known interaction — see the full K2/spice list.

See the full K2/spice interactions page
See every supplement checked against Primidone, ranked by severity
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Keep exploring
K2/spice monograph › Uses, safety, and every drug interaction in one place Primidone supplement interactions › Every supplement checked against Primidone, ranked by severity Primidone drug information › The full plain-English guide to this medication Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking K2/spice and Primidone Together: Common Questions

Can you take K2/spice with Primidone?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the K2/spice and Primidone interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Primidone and K2/spice?

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.