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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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