Vet for high risk play. If you don't have the utmost trust in someone, control what you're putting in your own body and know where it all came from.
Check for interactions. Yes, this means sharing complete information about whatever medications the person getting drugged is on. No, the interactions are not always intuitive. Yes, this includes things like alcohol. Ideally, ask your doctor about interactions with whatever you're about to play with- they're trained in spotting interactions, you're probably not.
If you've checked the interactions yourself, assume you might have missed something. Even if you've gotten your doctor to check, be aware they might have missed something. I once caught a potassium deficiency issue in someone's existing medication that their doctor prescribed them.
ROUND 1- Use it for its own sake before you play with it. Spend the time together and set yourself up for success: easy access to food, water, comfort media, and comfortable places to sit and lie down. Know how long it should last. Get someone who's used it before to tripsit if you can. Don't give yourself any tasks that involve new skills. Be ready to offer yourself or your partner a redirect from negative or anxious trains of thought.
Know what a good time on your drug physically looks and feels like. This is crucial, because things might go sideways in a way you're not expecting. Don't just be watching for specific signs of an overdose (though those are worth keeping in mind too)- if something seems wrong, get help. Seconds matter and you're probably not a professional.
Similarly: if the drug is at all sedative, or a downer, or long-lasting, and they're unconscious before it's out of their system, check for breathing and check for pulse. Also, your risk profile is your own, but I don't fuck around with hard sedatives- there's too fine a line between which body systems they shut down.
Start with a low-to-standard dose, and adjust doses for any relevant interactions (e.g. estradiol approximately halves liver tolerance [alcohol, weed, diphenhydramine], SSRIs approximately double psychedelic tolerance).
In order to avoid dependence issues, I wait a default of two weeks between recreational uses of any drug. (I only count caffeine here if I'm having more than two cups of tea in a day.)
ROUND 2- Play with it scripted and above board before you play with it in an explicitly cnc way. Your communication and mental state will have shifted, and you'll need to learn to accommodate that; make sure you try things out without added communication barriers first. Also, make sure to talk about how everything went afterwards when you're both sober!
If you're going to adjust doses, do it slowly and carefully. Most easily accessible recreational drugs can be incremented by half the standard dose. Some drugs are incredibly sensitive to fine adjustments; this is why Fentanyl, for example, is so dangerous and not recommended to use.
ROUND 3- Don't get comfortable. Try to have as peaceful and relaxed an experience as you want, and keep an eye on things as you play with different emotional states- but DEFINITELY continue to keep an eye on safety. It doesn't stop being a concern because you've done it once and everything went fine.
ETA- Mind how drugs affect things like pain tolerance! You might miss important signals from your body. Also, pay attention to overlap with your neurotype when planning and risk profiling. You might desire or achieve different effects depending on your own specific brain.
