lilbitcrazy
Bluelighter
- Joined
- Sep 20, 2021
- Messages
- 42
Conclusion:
Wow, I hope this lasts as it’s the best combination of medications I’ve tried in the last 20 years, I couldn’t find any research or anecdotal reports online and I was hesitant to commence. Apart from the mild cognition difficulties and some constipation, there are no other side-effects. I’ll follow-up with a blood test for liver enzyme markers in the near future.
Introduction:
A short anecdotal report, purely subjective, conducted over 30 days on a non-neurotypical subject (me), so take this with a grain of salt.
Background:
I have been taking Bupropion 300mg XL for 4 years now, recently I began experiencing severe side-effects (anger, irritability, agitation, breakthrough episodes) that caused me to discontinue, consequently, my negative schizoaffective symptoms re-emerged and I began researching for a solution.
Memantine is used off-label as a mood stabilizer but causes an interaction with Bupropion, each medication strongly inhibits the other’s specific metabolizer (CYP2B6 & CYP2D6 respectively) potentially concentrating the plasma levels and altering the half-life of the active drug.
Bupropion is quickly metabolized to hydroxybupropion which is a strong NET inhibitor with a half-life of 19 hours, I reasoned the side-effects were due to the build-up of norepinephrine and saw promise in the interaction with Memantine, by blocking the breakdown of Bupropion thereby increasing its DAT inhibitor effectiveness, Memantine is also a partial D2 agonist and NMDA antagonist so this combination may bode well?
Method:
Day 1 – Fasting 18 hours, 10mg of Memantine and the usual 300xl Bupropion. 1 Hour-in, mild euphoria, drowsiness, blurred vision and a little disassociation, cognitive clouding (specifically mental arithmetic, word recall and spelling difficulties) which is reported to pass after a few weeks of continuous usage.
(Rinse/repeat and fast-forward to reach steady state plasma level of Memantine)
Day 21 – Fasted state, (bump) 20mg Memantine + 300xl Bupropion, moderate disassociation, gradual and prolonged deep waves of euphoria, body-high and a stimulating trippy-like experience (like a low dose of LSD), I stayed home as it didn’t feel safe to drive and I wanted to isolate, the effects lasted 10 - 12 hours then gently faded. I decided to go back to 10mg per day as I wasn’t trying to get high but stable.
Day 30 – Fasted state, 10mg Memantine etc. Deep sense of well-being, calmness, relaxed, cognitive problems are much reduced, in fact cognition seems to be a little enhanced though that may be placebo, all in all this is a successful outcome and the original Bupropion side-effects are gone.
Discussion:
Seizure risk: Bupropion was taken off the market for a time due to its effect on reducing the seizure threshold. It's now thought that the maximum safe dose for an adult is in the range of 450mg - 600mg per day. As mentioned, Memantine may amplify the Bupropion plasma volume by inhibiting CYP2B6, so how might this affect the seizure threshold? I found one citation stating that "the norepinephrine effect of hydroxybupropion (HB) may cause seizures", so does reducing the creation of the pro drug HB and leaving a greater volume of circulating Bupropion mitigate the risk? Further, Bupropion has a shorter half-life (11 hours) than HB and works on the DAT channel increasing the duration of dopamine in the synaptic cleft so might it combine well with Memantine to de-risk seizures?
Cognition: Other concerns are around the antagonism of the different sets of Muscarinic (acetylcholine) receptors by each medication, it's been stated for Bupropion, that this accounts for its antidepressant effects, for Memantine it's believed that this causes the initial cognitive problems, however, since these receptors up-regulate quickly it's not considered a serious problem. Interestingly, each medication has been flaunted as a potential nootropic, so might they consolidate in combination?
Thank you for reading!
Bibliography
Convulsive liability of bupropion hydrochloride metabolites in Swiss albino mice
Results: All metabolites were associated with a greater percentage of seizures compared to bupropion, but the percentage of convulsions differed between metabolites. Hydroxybupropion HCl treatment induced the largest percentage of convulsing mice (100% at both 50 and 75 mg/kg) followed by threohydrobupropion HCl (50% and 100%, and then erythrohydrobupropion HCl (10% and 90%, compared to bupropion HCl (0% and 10%
https://pubmed.ncbi.nlm.nih.gov/18922171/
Bupropion: a review of its mechanism of antidepressant activity
Conclusion: The mechanism of action of bupropion appears to have an unusual, not fully understood, noradrenergic link. The bupropion metabolite hydroxybupropion probably plays a critical role in bupropion's antidepressant activity, which appears to be predominantly associated with long-term noradrenergic effects. The mild central nervous system activating effects of bupropion appear to be due to weak dopaminergic mechanisms. There is some evidence that dopamine may contribute to bupropion's antidepressant properties. Antidepressant effects of bupropion are not serotonergically mediated.
https://pubmed.ncbi.nlm.nih.gov/7665537/
Inhibitory effects of memantine on human cytochrome P450 activities: Prediction of in vivo drug interactions
The aim of the present study was to predict the drug interaction potential of memantine by elucidation of its inhibitory effects on cytochrome P450 enzymes using pooled human liver microsomes (HLM) and recombinant P450s. The inhibitory potency of memantine on CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 activities was examined with specific
https://www.researchgate.net/public...ities_Prediction_of_in_vivo_drug_interactions
Bupropion and its metabolites are inhibitors of CYP2D6, with hydroxybupropion responsible for most of the inhibition. Additionally, bupropion and its metabolites may decrease expression of CYP2D6 in the liver. The end effect is a significant slowing of the clearance of other drugs metabolized by this enzyme.[5] For instance, bupropion has been found to increase area-under-the-curve of desipramine, a CYP2D6 substrate, by 5-fold.[81
When people on bupropion are given MDMA, about 30% increase of exposure to both drugs is observed, with enhanced mood but decreased heart rate effects of MDMA.[83][84]
https://en.wikipedia.org/wiki/Bupropion
Memantine agonist action at dopamine D2High receptors
https://pubmed.ncbi.nlm.nih.gov/18000814/
Memantine-induced dopamine release in the prefrontal cortex and striatum of the rat--a pharmacokinetic microdialysis study
https://pubmed.ncbi.nlm.nih.gov/7813574/
Wow, I hope this lasts as it’s the best combination of medications I’ve tried in the last 20 years, I couldn’t find any research or anecdotal reports online and I was hesitant to commence. Apart from the mild cognition difficulties and some constipation, there are no other side-effects. I’ll follow-up with a blood test for liver enzyme markers in the near future.
Introduction:
A short anecdotal report, purely subjective, conducted over 30 days on a non-neurotypical subject (me), so take this with a grain of salt.
Background:
I have been taking Bupropion 300mg XL for 4 years now, recently I began experiencing severe side-effects (anger, irritability, agitation, breakthrough episodes) that caused me to discontinue, consequently, my negative schizoaffective symptoms re-emerged and I began researching for a solution.
Memantine is used off-label as a mood stabilizer but causes an interaction with Bupropion, each medication strongly inhibits the other’s specific metabolizer (CYP2B6 & CYP2D6 respectively) potentially concentrating the plasma levels and altering the half-life of the active drug.
Bupropion is quickly metabolized to hydroxybupropion which is a strong NET inhibitor with a half-life of 19 hours, I reasoned the side-effects were due to the build-up of norepinephrine and saw promise in the interaction with Memantine, by blocking the breakdown of Bupropion thereby increasing its DAT inhibitor effectiveness, Memantine is also a partial D2 agonist and NMDA antagonist so this combination may bode well?
Method:
Day 1 – Fasting 18 hours, 10mg of Memantine and the usual 300xl Bupropion. 1 Hour-in, mild euphoria, drowsiness, blurred vision and a little disassociation, cognitive clouding (specifically mental arithmetic, word recall and spelling difficulties) which is reported to pass after a few weeks of continuous usage.
(Rinse/repeat and fast-forward to reach steady state plasma level of Memantine)
Day 21 – Fasted state, (bump) 20mg Memantine + 300xl Bupropion, moderate disassociation, gradual and prolonged deep waves of euphoria, body-high and a stimulating trippy-like experience (like a low dose of LSD), I stayed home as it didn’t feel safe to drive and I wanted to isolate, the effects lasted 10 - 12 hours then gently faded. I decided to go back to 10mg per day as I wasn’t trying to get high but stable.
Day 30 – Fasted state, 10mg Memantine etc. Deep sense of well-being, calmness, relaxed, cognitive problems are much reduced, in fact cognition seems to be a little enhanced though that may be placebo, all in all this is a successful outcome and the original Bupropion side-effects are gone.
Discussion:
Seizure risk: Bupropion was taken off the market for a time due to its effect on reducing the seizure threshold. It's now thought that the maximum safe dose for an adult is in the range of 450mg - 600mg per day. As mentioned, Memantine may amplify the Bupropion plasma volume by inhibiting CYP2B6, so how might this affect the seizure threshold? I found one citation stating that "the norepinephrine effect of hydroxybupropion (HB) may cause seizures", so does reducing the creation of the pro drug HB and leaving a greater volume of circulating Bupropion mitigate the risk? Further, Bupropion has a shorter half-life (11 hours) than HB and works on the DAT channel increasing the duration of dopamine in the synaptic cleft so might it combine well with Memantine to de-risk seizures?
Cognition: Other concerns are around the antagonism of the different sets of Muscarinic (acetylcholine) receptors by each medication, it's been stated for Bupropion, that this accounts for its antidepressant effects, for Memantine it's believed that this causes the initial cognitive problems, however, since these receptors up-regulate quickly it's not considered a serious problem. Interestingly, each medication has been flaunted as a potential nootropic, so might they consolidate in combination?
Thank you for reading!
Bibliography
Convulsive liability of bupropion hydrochloride metabolites in Swiss albino mice
Results: All metabolites were associated with a greater percentage of seizures compared to bupropion, but the percentage of convulsions differed between metabolites. Hydroxybupropion HCl treatment induced the largest percentage of convulsing mice (100% at both 50 and 75 mg/kg) followed by threohydrobupropion HCl (50% and 100%, and then erythrohydrobupropion HCl (10% and 90%, compared to bupropion HCl (0% and 10%
https://pubmed.ncbi.nlm.nih.gov/18922171/
Bupropion: a review of its mechanism of antidepressant activity
Conclusion: The mechanism of action of bupropion appears to have an unusual, not fully understood, noradrenergic link. The bupropion metabolite hydroxybupropion probably plays a critical role in bupropion's antidepressant activity, which appears to be predominantly associated with long-term noradrenergic effects. The mild central nervous system activating effects of bupropion appear to be due to weak dopaminergic mechanisms. There is some evidence that dopamine may contribute to bupropion's antidepressant properties. Antidepressant effects of bupropion are not serotonergically mediated.
https://pubmed.ncbi.nlm.nih.gov/7665537/
Inhibitory effects of memantine on human cytochrome P450 activities: Prediction of in vivo drug interactions
The aim of the present study was to predict the drug interaction potential of memantine by elucidation of its inhibitory effects on cytochrome P450 enzymes using pooled human liver microsomes (HLM) and recombinant P450s. The inhibitory potency of memantine on CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 activities was examined with specific
https://www.researchgate.net/public...ities_Prediction_of_in_vivo_drug_interactions
Bupropion and its metabolites are inhibitors of CYP2D6, with hydroxybupropion responsible for most of the inhibition. Additionally, bupropion and its metabolites may decrease expression of CYP2D6 in the liver. The end effect is a significant slowing of the clearance of other drugs metabolized by this enzyme.[5] For instance, bupropion has been found to increase area-under-the-curve of desipramine, a CYP2D6 substrate, by 5-fold.[81
When people on bupropion are given MDMA, about 30% increase of exposure to both drugs is observed, with enhanced mood but decreased heart rate effects of MDMA.[83][84]
https://en.wikipedia.org/wiki/Bupropion
Memantine agonist action at dopamine D2High receptors
https://pubmed.ncbi.nlm.nih.gov/18000814/
Memantine-induced dopamine release in the prefrontal cortex and striatum of the rat--a pharmacokinetic microdialysis study
https://pubmed.ncbi.nlm.nih.gov/7813574/
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