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Antidepressants and Recreational Drugs (long!)

fairnymph

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FAQ: Antidepressants and Recreational Drugs (long!)

FAQ: Antidepressants and Recreational Drugs
(including pharmaceuticals of recreational value)

[Edit: Fixed vB coding in many posts after the upgrade, also deleted some innocuous posts. Awesome work, by the way - Orlando]

DISCLAIMER: This drug interaction table is based on medical literature, anecdotal,
and theoretical data gathered by author and is not necessarily accurate. The author
can not be held responsible for possible inaccurate/incorrect data.

Antidepressants (ADs) can be roughly categorized into five groups: Tricyclics, Heterocyclics, NARIs, SSRIs, and MAOIs.
Please take a moment to find the antidepressant you are curious about in the list below. Brand names are listed in parentheses after each drug, and the half-lives are listed in brackets. Once you have found what group your antidepressant belongs to, you can proceed to the section about that particular group of antidepressants to learn about recreational drug interactions. It might also be helpful to you the search function in your browser to find the name of your medication (make sure to spell it correctly!).

I have also provided some background information about ADs to satiate any general curiosity you might have about your medication.

Some information that might be of use when reading this FAQ:
Serotonin = 5-HT (5-hydroxytryptamine)
Noradrenaline = Norepinephrine = NE
Dopamine = DA
Neurotransmitter = NT
A Reuptake Inhibitor= a drug which prevents the reuptake of a neurotransmitter (such as serotonin, dopamine, etc), resulting in higher levels of the NT in the synapse
Agonist = a drug which STIMULATES the production or the uptake of an NT
Antagonist = a drug which INHIBITS the production or the uptake of an NT
Selectivity = refers to the ability of a drug to target only a certain kind of receptor. For example, Prozac is an SSRI (SELECTIVE serotonin reuptake inhibitor), which means that it ONLY inhibits serotonin reuptake, and does not affect other NTs. Effexor, on the other hand, is a SNRI ( a serotonin/norepinephrine reuptake inhibitor) � it is not �selective� because it affects more than one NT.

GENERAL NOTE: You can smoke weed/MARIJUANA/cannabis on any antidepressant. This is almost always a safe combination. Of course, if you are suffering any bad effects from smoking weed while on your medication, STOP smoking the weed.

Tricyclics (TCAs)
Amitripyline (Elavil, Endep, Tryptin(e,) Tryptanol)[31-46 hours]
Amitriptyline and Chlordiazepoxide (Limbitrol)
Amitriptyline + Perphenazine (brand name Etrafon, Triavil -- Perphenazine is an antispychotic)
Clomipramine (Placil, Anafranil)[22-84 hours]
Desipramine (Norpramin, Pertofran)[12-50 hours]
Dothiepin (Prothiaden, Dothep) [11-40 hours]
Doxepin (Adapin, Sinequan, Deptran)[8-24 hours]
Imipramine (Melipramine, Tofranil)[9-24 hours]
Lofepramine (Gamanil, Lomont) [extensively metabolized to Desipramine] [4-6 hours + ~24 hours for the desipramine metabolite]
Nortriptyline (Pamelor, Alledgron, Nortrilen, Sensival) [18-93 hours]
Protriptyline (Vivactil)[54-124 hours]
Trimipramine (Surmontil)[8-30 hours]

SSRIs
Citalopram (Celexa, Cipramil,Seropram) [23-75 hours]
Fluoxetine (Prozac, Flux, Fluxil, Fluxine, Modipran, Oxetin. Prolert, Prozyn, Rize, Seronil, Ufrex,Vonder, Zauxit) [72-360 hours]
Fluvoxamine (Luvox, Faverin, Dumirox) [7-63 hours]
Paroxetine (Paxil, Aropax, Seroxat) [3-65 hours]
Sertraline (Zoloft, Lustral, Besitran) [10-35 hours]

MAOIs (2 subtypes: Irreversible and Reversible)

Irreversible N.B.: half-lives not included because they mean very little in the case of irreversible MAOIs.
Chlorgyline [selective for MAO-A]
Isocarboxazid (Marplan) [nonselective]
Nialamide [nonselective]
Pargyline (Eutonyl) [nonselective]
Phenelzine (Nardil) [nonselective]
Rasagiline [selective for MAO-B]
Selegiline (Deprenyl) [selective for MAO-B]
Tranylcypromine (Parnate) [nonselective]

Reversible [all are selective for MAO-A, thus RIMAs]
Befloxatone
Brofaromine (Consonar)
Harmaline + Harmine
Moclobemide (Aurorex, Aurorix, Arima, Manerix)

Heterocyclics
Amoxapine (Asendin, Asendas) [8-14 hours]
Bupropion (Wellbutrin, Zyban, Zyntabac) [8-24 hours]
Mianserin (Bolvidon, Lantanon, Lerivon, Lumin, Norval, Tolvon) [17 (6-40) hours]
Mirtazapine (Remeron, Avanza, Rexer Zipsin) [20-40 hours]
Nefazodone (Serzone) [2-18 hours]
Tianeptine (Ardix, Stablon) [2.5 hours]
Trazodone (Desyrel) [4-14 hours]
Venlafaxine (Effexor) [4-10 hours]

NorAdrenaline Reuptake Inhibitors (NARIs)/Selective NE Reuptake Inhibitors
Atomoxetine (Strattera) [~5 hours]
Maprotiline (Ludiomil, Loxapac) [21-58 hours]
Reboxetine (Edronax, Vestra, Norebox) [8-18 hours]

TCAs/Tricyclics
Mechanism of Action
TCAs work by blocking the reuptake pumps of various NTs; most TCAs affect primarily the reuptake of serotonin and norepinephrine. By reducing the reuptake of these NTs, TCAs increase the levels of NTs in the synapse. Thus, TCAs are thought to increase the levels of 5-HT/NE/DA in the brain. The main difference in action between TCAs and SSRIs is that that only SSRIs selectively act on serotonin reuptake.

It is possible to become physically dependent on TCAs; thus if you stop taking TCAs suddenly, you might suffer withdrawal symptoms.

Common Side Effects
Sedation/fatigue, tremor, insomnia, blurred vision, constipation, urinary hesitancy, confusion, orthostatic hypotension, conduction defects, arrhythmias, aggravation of psychosis, seizures, weight gain, sexual dysfunction (inability to orgasm and decreased libido).

Metabolism
TCAs are rapidly absorbed and metabolized. CYP2C19 is the most important enzyme involved in the metabolism of TCAs, but the enzymes CYP 1A2, 3A4, 2C9 and CYP 2D6 are also involved.

Recreational Drug Interactions
Alcohol, GHB (and related substances), Benzos (Xanax, Valium, Klonopin etc), Opiates (Heroin, Codeine, Vicodin, Oxy etc), Barbituates: Because TCAs have strong sedative effects, combining TCAs with central nervous system (CNS) depressants like the drugs listed above can potentiate (make stronger) the effects of those drugs. I.e., if you are taking a TCA, you will be MORE SENSITIVE to these drugs, and you won't need to take as much to get fucked up. Therefore, please dose carefully; you will probably need a lower dose than a normal person. Otherwise, these drugs are fairly safe to combine with a TCA.

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

DXM (Dextromethorphan, Robotussin): This can be a very DANGEROUS combination! Do not take DXM and TCAs together! Combining DXM with a TCA can lead to too much serotonin in your brain, which can cause the potentially FATAL serotonin syndrome.

MDMA/Ecstasy (includes MDA, MDEA etc): TCAs will reduce the effects of taking MDMA, i.e. you won't roll very hard, if at all. Some people do roll on TCAs however, and find that TCAs do not inhibit the effects of MDMA as much as the SSRIs do. Still, you will find that rolling on TCAs is not NEARLY as fun as rolling without being on a TCA. It is not fatally dangerous to take MDMA while one TCA, but as MDMA increases the risk of cardiovascular complications, and TCAs already have some negative effects on the cardiovascular system, it could be unsafe to combine these drugs. I have not heard of a case of cardiovascular problems resulting from MDMA and TCA, but it is still a possibility that you should be aware of. Consider the combination of MDMA and a TCA very carefully; you'll find that it's probably not worth it.

Amphetamines (Methamphetamine, Adderall, Dexedrine), Ritalin (methylphenidate), Cocaine, 4-MAR (4-methylaminorex, sometimes called 'ice' or 'euphoria')
As with MDMA above, many people find that while they are on a TCA, they do not experience the full effects of these stimulants. However, you WILL still be able to get fairly high from these drugs; the impact of the TCA on your high will not be that great. The only danger here is the same as the danger above with MDMA; possible cardiovascular complications. If you combine stimulants and a TCA, watch your dosage and pay attention to any cardiovascular effects that seem unusual or disturbing.

Hallucinogens (LSD/Acid, psilocybin/Shrooms, Tryptamines, 2-ct-2,DPT, DMT etc, Salvia): TCAs can make the effects of hallucinogens stronger, therefore you should be careful about how much you take of a drug. You probably won't need as much to get high. Also, because hallucinogens have a number of cardiovascular effects, the same warning that applies to MDMA and stimulants applies here as well. Though fundamentally a safe combination, be careful and use moderation. Start with a LOW dose.

NOTE: Do not take 'ayahuasca' while on TCAs. This is a very dangerous combination.
 
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SSRIs
Mechanism of Action
SSRIs (Selective Serotonin Reuptake Inhibitors) work by selectively inhibiting the reuptake of serotonin. Thus, more serotonin remains for a longer period of time in the synapses. Although the different SSRIs vary in how effective they are at inhibiting 5-HT reuptake, they all do so selectively, and thus they do NOT have a direct (significant) effect on other NTs.

Common Side Effects
Insomnia, sedation (thought not nearly as severe as with the TCAs), tremor, gastronintestinal problems, rashes, sexual dysfunction (decreased libido and difficulty orgasming), acute anxiety.

Metabolism
SSRIs inhibit, to varying degrees, the enzymes CYP1A2, CYP2C19, CYP3A4 and CYP2D6. SSRIs and their metabolites can take a long time to completely leave the body. The issue with SSRIs is that in addition to the immediate effect they have on the brain, they also alter the brain in such a way that it takes some time after going off the SSRI for the brain to return to its normal configuration. How much a person's brain has been altered (and thus how long it will take for their brain to become normal again, and thus able to feel the full effects of MDMA), depends on the dose of the SSRI the person was taking, as well as the length of time the person was taking it for. So you can see, the time the person needs to be off an SSRI in order to, say, roll effectively will vary greatly from person to person. And that's not even taking into account a person's unique brain chemistry and metabolism.

Recreational Drug Interactions
Alcohol, GHB (and related substances), Benzos (Xanax, Valium, Klonopin etc), Opiates (Heroin, Codeine, Vicodin, Oxy etc), Barbituates, Ketamine: All of these drugs can be safely combined with SSRIs. You might be slightly more sensitive to alcohol, benzos, and barbituates (i.e.,they might fuck you up more than usual), otherwise, you should experience the drug as you would normally. Some people find that ketamine and opiates do not affect them as strongly.

DXM (Dextromethorphan, Robotussin): This can be a very DANGEROUS combination! Do not take DXM and SSRIs together! Combining DXM with an SSRI can lead to too much serotonin in your brain, which can cause the potentially FATAL serotonin syndrome.

MDMA/Ecstasy (includes MDA, MDEA etc): It is NOT POSSIBLE TO ROLL while taking an SSRI! It is a COMPLETE and UTTER WASTE OF YOUR MONEY! Basically, SSRIs 'block' the part of your brain where the MDMA needs to go in order to get you high; and since MDMA can't get in there, you won't be able to get high. You might experience some weak 'speedy' effects from high doses of MDMA, but you will not be able to truly 'roll'.

Do NOT stop taking your SSRI so that you can roll. First of all, even if you stop taking it for a few days, it is unlikely that you will fully be able to roll. It takes much longer than a few days for all the SSRI (and its metabolites and effects) to leave your body (read above under 'metabolism'). Second, you can get VERY SICK (withdrawal symptoms, depression, etc) if you stop taking your medicine. I strongly suggest that you give up rolling while you are taking an SSRI.

Amphetamines (Methamphetamine, Adderall, Dexedrine), Ritalin (methylphenidate), Cocaine, 4-MAr (4-methylaminorex, sometimes called 'ice' or 'euphoria'): The effects of these drugs on someone taking an SSRI will not be significantly different. With the amphetamines, especially methamphetamine, there will be less 'loveyness' but overall, the high will remain unchanged. This is a safe combination overall, and you should still be able to get high from these stimulants while on an SSRI.

Hallucinogens (LSD/Acid, psilocybin/Shrooms, Tryptamines, 2-ct-2,DPT, DMT etc, Salvia): These drugs can be safely combined with the SSRIs. Most people report that they need to take MORE of a hallucinogen to get normal effects. Thus, if you are taking an SSRI, you will probably need more of the drug to reach threshold effects. Some people find that they need to take more LSD, but that shrooms affect them normally. So be careful to start at a normal dose and only take more if you find that you need to.
NOTE: Do not take 'ayahuasca' while on an SSRI. Do not combine SSRIs with any kind of MAOI, such as harmaline.

MAOIs
Mechanism of Action
MonoAmine Oxidase Inhibitors are drugs with inhibit the enzyme Monoamine Oxidase. Monoamine Oxidase is the enzyme responsible for breaking down amines in the human body, and since NTs like serotonin, dopamine, and norepinephrine all have an amine group, they are all broken down by the MAO enzyme. Since MAOIs reduce or prevent MAO from breaking down the NTs, the NTs remain in the synapse longer (also, NT levels build in the presynaptic vesicles, so that MORE NTs are release). The end effect thus, of a MAOI, is higher levels of various NTs.
There are two MAOs: i.e., two enzymes responsible for the breakdown of NTs. There is MAO-A, an enzyme which breaks down various amines, including serotonin and norepinephrine, as well a tyramine, a byproduct of the conversion of tryptophan to 5-HT. Then there is MAO-B, an enzyme which breaks down dopamine. Some MAOIs work by inhibiting only one kind of MAO, and some MAOIs have inhibitory affects on both kinds of MAO.
MAOIs can also be either REVERSIBLE or IRREVERSIBLE. Irreversible MAOIs bind permanently to the MAO enzyme and prevent MA breakdown for up to two weeks after taking one dose of the MAOI. Reversible MAOIs do not bind to the MAO enzyme and their effects last only for a couple of days.

Common Side Effects
Sleep disturbances (either insomnia or fatigue/sedation), weight gain, postural hypertension (high blood pressure), sexual dysfunction.

Metabolism
Though MAOIs are metabolized and eliminated fairly rapidly, the inhibition of MAO can persist long after the MAOI can no longer be detected in the body. Thus, metabolism here is not nearly as important as the actual, more long-term effects of taking a MAOI.

Recreational Drug Interactions
Alcohol: If you are taking a MAOI, it is best to avoid Chianti wine and vermouth, as well as imported beer and ale. Consumption of red, white, and port wine in quantities less than 120ml present little risk. Whisky and liqueurs such as Drambuie and Chartreuse have also caused reactions. Best to stick with drinks like vodka, gin, rum etc and to avoid imported beers and red wine.

GHB (and related substances),Benzos (Xanax, Valium, Klonopin etc) and Barbiturates: While you can take these drugs while on a MAOI, please be very careful when doing so and take LOW DOSES. MAOIs cause hypErtension while benzos/barbs cause hypOtension, and thus you can confuse and upset your heart rate, blood pressure etc by combining the two drugs.

Opiates (Heroin, Codeine, Vicodin, Oxy etc): It is NOT SAFE to use opiates while on a MAOI. Combining these drugs could lead to hyper or hypotensive crises, as well as respiratory complications. Avoid these drugs if you are taking a MAOI, PLEASE!

Ketamine: It is safe to use ketamine while taking a MAOI.

DXM (Dextromethorphan, Robotussin): This can be a very DANGEROUS combination! Do not take DXM and MAOIs together! Combining DXM with a MAOI can lead to too much serotonin in your brain, which can cause the potentially FATAL serotonin syndrome. If you are on a MAOI that is selective for MAO b, such as rasagiline or selegiline (l-deprenyl), then it is safe to use DXM.

MDMA/Ecstasy (includes MDA, MDEA etc): A VERY DANGEROUS combination. Do not roll while you are taking a MAOI. This leads to serotonin syndrome, a hypertensive crisis, and eventually death. A number of people have DIED from combining MDMA and a MAOI. DO NOT DO THIS! If you are on a MAOI that is selective for MAO b, however, such as rasagiline or selegiline (l-deprenyl), then it is safe to use MDMA, and in fact the MAO b inhibitors have been shown to reduce MDMA-related neurotoxicity. The same goes for the stimulants discussed in the next paragraph.

Amphetamines (Methamphetamine, Adderall, Dexedrine), Ritalin (methylphenidate), Cocaine, 4-MAR (4-methylaminorex, sometimes called 'ice' or 'euphoria'): Again, a DANGEROUS combination, pretty much like combining MDMA and a MAOI. Stay away from stimulants when taking a MAOI!

Hallucinogens (LSD/Acid, psilocybin/Shrooms, Tryptamines, 2-ct-2,DPT, DMT etc, Salvia): Apparently, people taking MAOIs are LESS sensitive to hallucinogens/tryptamines than normally. This is especially true with LSD. Interactions with the tryptamines and with salvia are not well established, so please be VERY CAREFUL when combining. Start out with a LOW DOSE and see how the drug affects you before proceeding.

Reversible MAOIs:: If you are taking a RIMA, do not use recreational drugs that are warned against in this FAQ within SEVEN DAYS of going on or off your medication. I.e., if you get high on a contraindicated drug (this means a drug that you can't take on a RIMA), you should wait 7 days before starting to take your medicine. If you STOP taking your RIMA, you should be off the medicine for at least 7 days before you attempt to get high.

Irreversible MAOIs If you are taking an irreversible MAOI, you need to abstain from drug for a week before starting your medication. If you are going OFF an irreversible MAOI, you need to avoid recreational drugs for THREE WEEKS. Please be careful and heed this advice, or severe medical problems and/or death are possible.
 
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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.
 
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Trazodone
Mechanism of Action
Trazodone has agonist activity at 5-HT2C receptors and potent antagonist activity at 5-HT2A receptors, and acts as a weak serotonin reuptake inhibitor. The effects of trazodone are dose-dependent: at low doses it acts as a 5-HT antagonist, whereas at higher doses it acts as a 5-HT agonist (related to the main metabolite CPP). It also antagonizes the alpha 1 and alpha 2 adrenergic receptors.

Common Side Effects
Drowsiness, dizziness, insomnia, nausea, agitation.

Metabolism
Trazodone is extensively metabolized by CYP34A to its active metabolite, m-chlorophenylpiperazine (mCPP). The enzyme CYP2D6 is also involved in the metabolism of trazodone.

Recreational Drug Interactions
Alcohol, GHB (and related substances), Benzos (Xanax, Valium, Klonopin etc), Opiates (Heroin, Codeine, Vicodin, Oxy etc), Barbiturates, Ketamine: Trazodone increases sensitivity to alcohol, benzos, opiates and barbiturates. It is likely that trazodone increases sensivity to ketamine as well, though this is a safe combination either way.

DXM (Dextremethorphan, Robotussin): Because DXM and trazodone are metabolized by some of the same enzymes, this combination is likely to be quite DANGEROUS. It is NOT recommended that you take these drugs together.

MDMA/Ecstasy (includes MDA, MDEA etc): Trazadone appears to reduce the effects of MDXX slightly.

Amphetamines (Methamphetamine, Adderall, Dexedrine), Ritalin (methylphenidate), Cocaine, 4-MAR (4-methylaminorex, sometimes called 'ice' or 'euphoria'): Trazodone and stimulants do not seem to interact in any way; thus combining these drugs is probably relatively safe.

Hallucinogens (LSD/Acid, psilocybin/Shrooms, Tryptamines, 2-ct-2, DPT, DMT etc, Salvia) Trazodone will probably reduce your sensitivity to hallucinogens.
Do NOT take trazodone with a MAOI of any sort! This is most likely a dangerous combination.

Venlafaxine
Mechanism of Action
Venlafaxine selectively inhibits the reuptake of both serotonin and norepinephrine, thus it is known as an SNRI.

Common Side Effects
Nausea, somnolence, sweating, dizziness, sexual dysfunction, insomnia, hypertension, anxiety.

Metabolism
Venlafaxine is extensively metabolized by CYP2D6 and somewhat metabolized by CYP3A4. It is also a weak inhibitor of the enzyme 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 venlafaxine, and there effects will not be significantly altered.

DXM (Dextromethorphan, Robotussin): Because DXM and venlafaxine are metabolized by some of the same enzymes, this combination is likely to be quite DANGEROUS. It is NOT recommended that you take these drugs together.

MDMA/Ecstasy (includes MDA, MDEA etc): See SSRIs. It is not possible to roll on venlafaxine. UNDER NO CIRCUMSTANCES should you STOP TAKING YOUR VENLAFAXINE SUDDENLY. Venlafaxine has VERY SEVERE WITHDRAWAL SYMPTOMS including nausea, dizziness, and ELECTRIC SHOCKS!

Amphetamines (Methamphetamine, Adderall, Dexedrine), Ritalin (methylphenidate), Cocaine, 4-MAR (4-methylaminorex): Amphetamines can be used relatively safely in combination with venlafaxine.. You should get normal effects from these drugs. Cocaine use is also relatively safe; however some people find that while they are taking venlafaxine they are MORE SENSITIVE to cocaine and that the cocaine high lasts longer. Ritalin, when taken by a person on venlafaxine, has been known to cause seizures, so use extreme caution with this combination.

Hallucinogens (LSD/Acid, psilocybin/Shrooms, Tryptamines, 2-ct-2, DPT, DMT etc, Salvia) Hallucinogens and venlafaxine can be relatively safely combined, without any significant impact on the effects of the hallucinogen being used.
Do NOT take venlafaxine with a MAOI of any sort! This is a VERY DANGEROUS combination that can lead to serotonin syndrome and death!

FAQ completed on 03/29/02 by fairnymph.

UPDATED on 11/24/03 with new information, added combinations with GHB and 4-MAR, and some typos corrected. - fairnymph
 
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I thought MAOIs incresed the effects of some tryptamines. For example ayahuasca and shroomhuasca (i.e. harmaline and shrooms). So shouldn't people taking MAOIs be extra carefull dosing with tryptamine substances?
[ 30 March 2002: Message edited by: chrisdoom ]
 
Re: MAOIs and tryptamines:
There doesn't seem to be a whole lot of conclusive information on this combination.Techinically ayahuasca refers to the combination of a MAOI and a tryptamine. In addition, a number of tryptamines have mild MAOI properties. Some tidbits:

...in a recent letter to MAPS, Jon Ott challenged the mechanism of MAOI in Ayahuasca, pointing out that though MAO inhibition in the gut would allow tryptamines to enter the bloodstream, MAOI in the brain actually has an antagonistic effect on LSD and DMT, as can be expected, and as has been seen in clinical tests with clinical MAOIs.
See this link.

The explanation that was given to me is as follows: a single dose of MAOI may potentiate tryptamines by allowing more of the tryptamines to get into the brain (the image I think of is that MAO is standing guard while DMT or some such tries to sneak past it - brofaromine, for example, can "distract" the MAO so the DMT can sneak by; phenelzine is more ruthless and just kills the guard!). However, after chronic dosing with an MAOI, serotonin receptors are apparently (would need to look this up to be sure) desensitized and their numbers decreased. This, combined with the extra serotonin that's floating around as a result of the MAOI, leaves little for the tryptamine to bind to (it's thought that tryptamines are some flavor of serotonin agonist and/or antagonist).

And yes, it is true that the effects of psychedelics in general seem to be much, much weaker if you've been taking an MAOI beforehand.
See here.

Travis:
Thank you! I really put alot of effort in this guide so I do hope that it is useful. I have also been self-experimenting (as in the case of reboxetine and currently with tianpetine) by combining the newer antidepressants with recreational drugs. Alot of the information WAS hard to find or just didn't exist, which was even more frustrating.

I'm very interested to hear about your venlafaxine and DXM combination. How many times have you combined these two? How much venlafaxine do you take daily and how long have you been taking it for? What doses of DXM have you been taking?

[ 01 April 2002: Message edited by: fairnymph ]
 
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"Hallucinogens (LSD/Acid, psilocybin/Shrooms, Tryptamines – 2-ct-2,DPT, DMT etc, Salvia) These drugs can be safely combined with
the SSRIs. Most people report that they need to take MORE of a hallucinogen to get normal effects. Thus, if you are taking an SSRI,
you will probably need more of the drug to reach threshold effects. Some people find that they need to take more LSD, but that
shrooms affect them normally. So be careful – start at a normal dose and only take more if you find that you need to.
NOTE: Do not take ‘ayahuasca’ while on an SSRI. Do not combine SSRIs with any kind of MAOI, such as harmaline."
Out of curiosity, about how many anecdotal reports of lessened LSD effects did
you see, and could you attempt to quantify the degree of sensitivity loss?
Adam "so, so confused" Blake
 
Fairnymph-
do you maybe have a link or info for me about the effects of rolling while on the anti seizure medication Topamax? (its an AED; antiepileptic, topiramate) I don't take it for seizures, but rather as a mood stabilizer (I have been diagnosed as bipolar)this info you've set up is absolutely fantastic, thank you for your time and efforts!!!!!
 
I'm very interested to hear about your venlafaxine and DXM combination. How many times have you combined these two? How much venlafaxine do you take daily and how long have you been taking it for? What doses of DXM have you been taking?
I started taking venlafaxine about a year ago, and, after some dose experimentation, I settled on 150 mg daily.

While on venlafaxine:
The highest dose of DXM I've taken is a 4 oz robo max and a few succrettes, which is about 400 mg total. That's a good solid 2nd plateau dose for me. I've taken 350 mg about 5 times. I've taken 1st plateau doses several times, and I've taken smaller doses countless times for bad coughs, flues, and such. The experiences I've had with the combination sound the same as those of people who don't take venlafaxine. I haven't tried higher doses of DXM, because I'm worried it might cause seritonin syndrom, and it also makes me think a little slower the next morning.

The product literature that came with the venlafaxine specifically said to be cautious when taking it with DXM, but my doctor said it wouldn't harm me to combine them.
 
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www.rxlist.com
www.erowid.org
[ 20 June 2002: Message edited by: fairnymph ]
 
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Effexor is not an SSRI, because by definition SSRIS (selective serotonin reuptake inhibitors) ONLY inhibit the reuptake of serotonin. Effexor also inhibits the reuptake of norepinephrine, which SSRIs do not significantly do. Thus, Effexor is an SNRI (serotonin norepinephrine reuptake inhibitor) and has properties of SSRIs as well as its own norepinephrine properties.
Because Effexor strongly inhibits the reuptake of serotonin, just like SSRIs do, it is not possible to roll on Effexor.
 
If anyone wants to check out a good 6 page article on the failure of antidepressants and the use of opiates for depression just google " future opioids the birth of a new generation ". The first 3 sentences go " A significant minority of the population only feel truly well on opioids. In effect, they self medicate, taking responsibility for thier own mental health in defiance of medical orthodoxy ". Its amazing how doctors will tell you (if you ask) that antidepressants are not addictive but you should cut down slowly.
 
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