HETEROCYCLICS



Amoxapine

Mechanism of Action

Amoxapine is a weak 5HT inhibitor and significantly inhibits reuptake NE. It is also a DA receptor antagonist. This drug increases the levels of serotonin and norepinephrine in the brain (much like tricyclics) and decreases dopamine levels, thus amoxapine can act as an antipsychotic (through its effects on dopamine) as well as an antidepressant.



Common Side Effects

Similar to the TCAs/tricyclics, see above.



Metabolism

Amoxapine is metabolized in the liver by the CYP2D6 enzyme.



Recreational Drug Interactions

Pretty much identical to the drug interactions for the tricyclics/TCAs, see above.



Bupropion



Mechanism of Action

Bupropion's mechanism of action is not fully understood, but current information indicates that it is a NE and DA reuptake inhibitor, and also acts as a weak 5HT reuptake inhibitor.



Common Side Effects

Dizziness, insomnia, dry mouth, sweating, tremor, aggravation of psychosis, potential for seizures at high doses. May increase libido, especially in women.



Metabolism

Several different CYP enzymes (i.e., CYP2B6, 3A4, 2A6, 2E1, and 1A2) can mediate the biotransformation of bupropion. Primarily metabolized by CYP2B6. Inihibits the enzyme CYP2D6.



Recreational Drug Interactions

Alcohol, GHB (and related substances), Benzos (Xanax, Valium, Klonopin etc), Opiates (Heroin, Codeine, Vicodin, Oxy etc), Barbituates, Ketamine: Some people taking bupropion have found that it does not combine well with acohol, and that they are more sensitive to alcohol and to blacking out while drinking. Not all people on bupropion find that alcohol affects them differently, however. Your best bet is to drink cautiously when you first start taking buproprion, and observe how alcohol affects you. All other downers (opiates, benzos, barbiturates) and ketamine are safe for people taking bupropion.



DXM (Dextromethorphan, Robotussin): Not much is known about the combination of bupropion and DXM, but it appears to be safe. Use caution until more is known; start with a low dose.



MDMA/Ecstasy (includes MDA, MDEA etc): There is a lot of controversy about rolling on bupropion. Some people (especially people who have bipolar) find that they can roll normally. Some people find that they roll slightly less hard than normally. Some people find that they only roll a little bit. In general, most people find that they can still roll, but not quite as hard, and so they often need to take more MDMA than usual. However, until you know how MDMA affects you personally while you are on bupropion, take your normal dose of MDMA. If you are at all prone to seizures, you should avoid combining bupropion and MDMA as you are more likely to suffer a seizure with this combination.



Amphetamines (Methamphetamine, Adderall, Dexedrine), Ritalin (methylphenidate), Cocaine, 4-MAR (4-methylaminorex): Amphetamines and ritalin are safe to use and the high should be unaffected. Some people on bupropion find that they get more out of cocaine; the high is better and lasts longer. In general, all stimulants seem to be safe for people taking bupropion. Observe, however, that if you are at all prone to seizures, you should avoid combining bupropion and stimulants as you are more likely to suffer a seizure with such a combination.



Hallucinogens (LSD/Acid, psilocybin/Shrooms, Tryptamines, 2-ct-2,DPT, DMT etc, Salvia) There are no known dangers resulting from combining these drugs with bupropion.



NARIs/NORADRENALINE REUPTAKE INHIBITORS



Mechanism of Action

Both drugs are selective noradrenaline (NA/NE) reuptake inhibitors, sometimes called NARIs.



Common Side Effects

Skin rash, redness, swelling, itching,nausea or vomiting, shakiness or trembling; seizures,unusual excitement, weight loss, blurred vision, dizziness or lightheadedness, drowsiness, dry mouth, headache, increased or decreased sexual drive, constipation,heartburn; increased appetite and weight gain, increased sensitivity of skin to sunlight; increased sweating, insomnia, weight loss.



Metabolism

Primarily metabolized by the enzyme CYP2D6.



Recreational Drug Interactions

Alcohol, GHB (and related substances), Benzos (Xanax, Valium, Klonopin etc), Opiates (Heroin, Codeine, Vicodin, Oxy etc), Barbituates: If you are taking a NARI, then the effects of these drugs might be stronger than normal. This is especially true when using barbiturates. Go easy on these drugs and stick to low doses until you are sure how they interact with the NARI. Otherwise these drugs are safe to use while on a NARI.



Ketamine: The effects of this drug should not be altered by NARIs and the combination is not known to be dangerous.



DXM (Dextromethorphan, Robotussin): Because NARIs and DXM are metabolized by some of the same enzymes, this combination is most likely quite dangerous. Avoid taking DXM and a NARI together!



MDMA/Ecstasy (includes MDA, MDEA etc): Not much is known about rolling on NARIs. Rolling is still possible, and appears to be safe. Some of MDMA's effects are intensified while other effects are absent or weakened. I was much hotter and more sedated than usual, and jaw clenching/grinding, which I normally don't suffer from much, was quite severe. I also felt more 'fucked up', I was more out of it, had trouble with motor control, walking, etc. I did not feel 'stimulated' and I did not experience body rushes and tingling like I normally do. I still felt a decent amount of euphoria, however, and was more social and talkative. The comedown from MDMA was unpleasant (which it has never been otherwise), and included headache and jaw pain.



Amphetamines (Methamphetamine, Adderall, Dexedrine), Ritalin (methylphenidate), Cocaine, 4-MAR (4-methylaminorex): While it is not particularily dangerous (according to current data, at least) combining NARIs and amphetamines/ritalin is not recommended. The stimulant effects of the drugs, i.e. feeling alert/awake/hyper etc, are almost completely blocked by the NARI. You can snort 3 fat lines of quality meth and fall asleep two hours later. Jaw clenching, headache, come down etc are all terrible. There are some fucked-up feelings but very little euphoria and the bad side effects override any pleasurable effects. Nothing is known about combining cocaine and a NARI but an interaction similar to the amphetamine/ritalin interaction is suspected. Interactions with 4-MAR would probably be milder and less worriesome, or possibly completely absent.



Hallucinogens (LSD/Acid, psilocybin/Shrooms, Tryptamines, 2-ct-2,DPT, DMT etc, Salvia) There are no known dangers resulting from combining these drugs with a NARI.



Mianserin

Mechanism of Action

Mianserin is an antagonist of both norepinephrine and serotonin receptors. Specifically, it is a 5HT1c, 5HT2a, and 5HT2c antagonist, as well as an antagonist of the NE alpha-2 receptor and the H1 (histamine) receptor. It does not inhibit the reuptake of any neurotransmitter at therapeutic dosages. There is evidence that 5-HT2C receptors are involved in the control of the activity of the central dopaminergic system, and thus it is thought that mianserin increases DA release in the nucleus accumbens by blocking 5-HT2C receptors.



Common Side Effects

Sedation/drowsiness, dizziness, constipation, dry mouth, blurred vision, weight gain. Negligible anticholinergic effects compared to most other ADs.



Metabolism

The most important enzymes involved in the metabolism of mianserin are CYP2D6, CYP1A2, and CYP3A.



Recreational Drug Interactions

Alcohol, GHB (and related substances), Benzos (Xanax, Valium, Klonopin etc), Opiates (Heroin, Codeine, Vicodin, Oxy etc), Barbituates: The effects of these drugs will be stronger than normal, as they will add to the sedative effects of mianserin. This is especially true of the benzos and opiates. BE CAREFUL and go easy on these drugs and stick to low doses until you are sure how they interact with the mianserin.



Ketamine: The effects of this drug should not be altered by mianserin and the combination is not known to be dangerous.



DXM (Dextromethorphan, Robotussin): Because mianserin and DXM are metabolized by some of the same enzymes, this combination is most likely quite dangerous. Avoid taking DXM and mianserin together!



MDMA/Ecstasy (includes MDA, MDEA etc): There is some evidence that mianserin may reduce MDMA-related neurotoxicity by blocking some of MDMA's effects on 5HT2 receptors. Mianserin's effects on NE probably increases the stimulant effects of MDMA. Though probably a relatively safe combination, roll with caution; start with a low dose.



Amphetamines (Methamphetamine, Adderall, Dexedrine), Ritalin (methylphenidate), Cocaine, 4-MAR (4-methylaminorex): Mianserin seems to potentiates (increase) the effects of stimulants. This means that you should be VERY CAREFUL when using stimulants stick to low doses until you have a better understanding of how these drugs interact with mianserin



Hallucinogens (LSD/Acid, psilocybin/Shrooms, Tryptamines, 2-ct-2,DPT, DMT etc, Salvia) Hallucinogens seem to be stronger on mianserin, so please dose carefully. It is probably not wise to combine mianserin with a MAOI-like hallucinogen, though not much is currently known about such interactions.



Mirtazapine

Mechanism of Action

Mirtazapine is an antagonist of presynaptic alpha 2-adrenergic autoreceptors and heteroreceptors on both norepinephrine and serotonin presynaptic axons. It is also is a potent antagonist of 5HT2 and 5HT3 receptors. As a result, there is increased NE and 5HT activity, especially increased 5HT activitity at the 5HT1A receptors.



Common Side Effects

Sedation, increased appetite, dizziness, and weight gain.



Metabolism

CYP2D6, CYP1A2, and CYP3A4 are the primary enzymes involved in the metabolism of mirtazapine.



Recreational Drug Interactions

Alcohol, GHB (and related substances), Benzos (Xanax, Valium, Klonopin etc), Opiates (Heroin, Codeine, Vicodin, Oxy etc), Barbituates: The effects of these drugs will be stronger than normal, as they will add to the sedative effects of mirtazapine. CAREFUL and go easy on these drugs and stick to low doses until you are sure how they interact with the mirtazapine.



Ketamine: The effects of this drug should not be altered by mirtazapine and the combination is not known to be dangerous.



DXM (Dextromethorphan, Robotussin): Because mirtazapine and DXM are metabolized by some of the same enzymes, this combination is most likely quite dangerous. Avoid taking DXM and mirtazapine together!



MDMA/Ecstasy (includes MDA, MDEA etc): Rolling on mirtazapine is relatively safe. Some people find that they do not roll quite as hard as they usually would, and that they need to take about 1/2 an extra pill to obtain normal effects.



Amphetamines (Methamphetamine, Adderall, Dexedrine), Ritalin (methylphenidate), Cocaine, 4-MAR (4-methylaminorex): Using stimulants while on mirtazapine seems to be relatively safe as well. The mirtazapine does not appear to affect the recreational effects of the stimulant (i.e. you will get just as high as you always did).



Hallucinogens (LSD/Acid, psilocybin/Shrooms, Tryptamines, 2-ct-2,DPT, DMT etc, Salvia) Hallucinogens seem to be MUCH stronger in combination with mirtazapine, so please be VERY CAREFUL! A dangerous interaction with shrooms has been observed in one person taking mirtazapine. Please avoid hallucinogens while taking mirtazapine or dose very carefully.



Nefazodone

Mechanism of Action

Nefazodone is a 5HT2 receptor antagonist and also antagonizes alpha1-adrenergic receptors. It appears to a be a weak serotonin reuptake inhibitor as well. Thus, nefazodone's AD properties probably share some similarilities with the TCAs/SSRIs and with drugs like mianserin and mirtazapine.



Common Side Effects

Sedation, dry mouth, nausea, dizziness, constipation, asthenia, lightheadedness, blurred vision, confusion, insomnia, agitation and abnormal vision.



Metabolism

Nefazodone inhibits the enzyme CYP3A4, and is metabolized by CYP2D6.



Recreational Drug Interactions

Alcohol, GHB (and related substances), Benzos (Xanax, Valium, Klonopin etc), Opiates (Heroin, Codeine, Vicodin, Oxy etc), Barbituates, Ketamine: These drugs can be safely combined with nefazodone. Of course, if you feel somewhat sedated from the nefazodone, it makes sense not to consume too much of a downer, so don't take more than you really need to.



DXM (Dextromethorphan, Robotussin): Because nefazodone and DXM are metabolized by some of the same enzymes, this combination is most likely quite dangerous. Avoid taking DXM and nefazodone together!



MDMA/Ecstasy (includes MDA, MDEA etc): Rolling on nefazodone is relatively safe. Because of the serotonin reuptake inhibitor effects of nefazodone, you will probably not roll as hard as usual. Some people will stop taking nefazodone for a day or two in order to roll more effectively. While stopping your medication is never recommended, in this case stopping for a day or two seemed to improve people's rolls.



Amphetamines (Methamphetamine, Adderall, Dexedrine), Ritalin (methylphenidate), Cocaine, 4-MAR (4-methylaminorex): Using stimulants while on nefazodone seems to be relatively safe as well. The nefazodone does not appear to affect the recreational effects of the stimulant (i.e. you will get just as high as you always did).



Hallucinogens (LSD/Acid, psilocybin/Shrooms, Tryptamines, 2-ct-2, DPT, DMT etc, Salvia) Not much is known about combining hallucinogens with nefazodone, but it is very likely that nefazodone makes the effects of hallucinogens stronger. You should therefore be very careful about combining nefazodone with hallucinogens; start with a low dose and be careful!



Tianeptine

Mechanism of Action

Tianeptine increases serotonin uptake thereby increases serotonin levels in the brain. How exactly this occurs is not known.



Common Side Effects

Gastralgia, abdominal pain, dryness of the mouth, anorexia, nausea, vomiting, flatulence, insomnia, drowsiness, nightmares, asthenia, tachycardia, extrasystole, precordialgia, dizziness, headaches, faintness, trembling, respiratory discomfort, tightness of the throat, myalgia, lumbago, changes in dreaming.



Metabolism

Tianeptine is not subject to first-pass hepatic metabolism, has high bioavailability and limited distribution, and is rapidly eliminated. It differs from most antidepressants in that it is not primarily metabolised by the hepatic cytochrome P450 system.



Recreational Drug Interactions

Alcohol, GHB (and related substances), Benzos (Xanax, Valium, Klonopin etc), Opiates (Heroin, Codeine, Vicoden, Oxy etc), Barbituates, Ketamine: These drugs can be safely combined with tianeptine. Ketamine seems very slightly potentiated/stronger.



DXM (Dextromethorphan, Robotussin): Not much is known about the combination of DXM and tianeptine. As it is somewhat likely that the combination is dangerous, use caution until more is known.



MDMA/Ecstasy (includes MDA, MDEA etc): AFAIK, I am the only person to have ever taken MDMA while taking tianeptine (37.5mg/day for a month). The combination was a good one, and undoubtably the tianeptine potentiated (made stronger) the effects of the MDMA. Having rolled a dozen times, on a variety of doses, I can say that this was the strongest roll I have ever experienced. The dose of MDMA was average for me, and it was pure and tested. The tianeptine does not potentiate the MDMA enough to make the combination really dangerous, but nonetheless I recommend being cautious when using MDMA while taking tianeptine. You certainly would not need to take more than 1-2 pills.



Amphetamines (Methamphetamine, Adderall, Dexedrine), Ritalin (methylphenidate), Cocaine, 4-MAR (4-methylaminorex, sometimes called 'ice' or 'euphoria'): Again, the only reference I can provide here is my own. I have used all of these substances except 4-MAR while on tianeptine, and the amphetamines seemed to be noticeably, though not overhwelmingly stronger, while my experiences with methylphenidate and cocaine were normal. The combination does not seem dangerous, but most likely you will need only an average dose of an amphetamine in order to feel the effects quite intensely.



Hallucinogens (LSD/Acid, psilocybin/Shrooms, Tryptamines, 2-ct-2, DPT, DMT etc, Salvia) Tianeptine and hallucinogens seem to be a safe combination. Psychedelic drugs appear to be slightly stronger than usual, but not by much.

Do NOT take tianeptine with a MAOI of any sort! This is most likely a dangerous combination.