[Epistemic Status: anecdotal data; this is not a list of “life hacks”; it is intended as a list of interesting research leads; don’t take drugs unless you really know what you are doing!]

I’ll mark to the right of each anecdata:

• n=x when I can remember clearly how many people have said this to me up to n = 10 (e.g. n=7 means that 7 people have told me this)
• n=x/y when I know that y people have tried it and of those x have experienced this
• n>1 when 1 < n < 10 but I don’t remember exactly how many people have said it, and
• pattern if it’s a pattern I’ve observed across more than 10 people pooled from online trip reports and conversations from email exchanges, forums, group chats, private messages, and things that have come up at IRL discussions (e.g. at festivals).

Psychedelics

The “best” phenethylamines in terms of the balance between mind expansion, euphoria, and low bodyload are:

• 2C-B (low bodyload, high euphoria, unlikely to freak out at <25mg) [pattern]
• 2C-C (like 2C-B but also relaxing, unlikely to freak out at <40mg) [pattern]
• 2C-D (particularly easy on the body relative to other phenethylamines, unlikely to freak out at <30mg) [pattern]
• 2C-I (more trippy and stimulating than the above, unlikely to freak out at <25mg) [pattern]

Among some of the worst 2Cs (but perhaps not worst phenethylamines) we find:

• 2C-P (particularly bad bodyload, inevitable vomiting above some dose) [pattern]
• 2C-E (“just too weird” for a lot of people, strong bodyload) [pattern]
• 2C-T-2 (high bodyload, strangely similar to LSD in headspace) [n>1]
• 2C-T-7 (same as 2C-T-2) [n>1]

IV Psychedelics

• Do not ever IV 2C-E as it leads to instant extreme crams, nausea, and general bodily discomfort. [n=1]
• The come-up of IV 2C-B is very fast relative to oral administration (5 minutes) and the peak is a lot more intense as well. 5mg results in an intensity of experience comparable to 35mg oral at its peak. [n=5]
• Within 10 minutes of IV 2C-B one feels an intense urge to defecate. [n=4/5]
• While IV 100μg LSD takes a full 30 minutes to show the start of effects, IV 300μg takes only 5 minutes to show pronounced effects. [n=1]
• Ketamine is reportedly experienced as a “completely different drug” when the ROA is IV vs. IM vs. intranasal. [pattern]
• IV Ketamine gives rise to a distinct metallic taste in one’s mouth within a few seconds of administration. [n>1]

Anti-Tolerance Drugs

In Anti-Tolerance Drugs we gave a list of drugs that, when taken in conjunction with painkillers and euphoric substances, can lessen, prevent, and even reverse tolerance. But “drug tolerance” is not a natural kind. Indeed, there are many systems of neuroadaptation that prevent drugs from exerting the same effect over time. Nothing makes this clearer than the typically life-long loss of “magic” to MDMA after a few experiences, which stands in contrast to the largely reversible tolerance to ethyl alcohol post-PAWS. Indeed, “drug tolerance” can mean tolerance to reduced action for: antidepressant effects (SSRIs), lessening chronic pain (opioids), increasing executive function (modafinil), enhancing motivation (amphetamine), “the magic” (ketamine, MDMA), the sense of unity and interconnectedness (LSD), otherworldliness (salvia), and so on. Indeed you can have a drug that generates tolerance to one of its effects but not others. For example, Slate Star Codex’s nootropic survey found that despite the common wisdom that prescription amphetamines stop generating a sense of euphoria after a while, most people who use them clinically for ADHD continue to experience an enhanced focus on the drug for many years. In this vein, the following anecdata highlights how anti-tolerance drugs have a much more subtle and multifaceted effect than just “reducing tolerance”:

• DXM and other dissociatives seem to potentiate both the analgesic and euphoric effects from opioids, increase constipation, and leave pruritus the same. [n>1]
• Proglumide reduces both the intensity of opioid withdrawal as well as the tolerance to their analgesic, sedative, and constipation effects. It does not affect euphoria or pruritus. [n>1]
• Ultra-low dose naltrexone (ULDN) reduces tolerance to analgesic and sedative effects from opioids but not euphoria (“it makes opioids more sleep-inducing but a lot less fun“). Interestingly, ULDN prevents constipation from opioids. [n>1]
• Black seed oil and ashwagandha reduce the tolerance to the analgesic, sedative, euphoric, and pruritus effects of opioids without influencing constipation. These effects are milder than all of the above. [n=1]
• Agmatine potentiates the analgesic effects of opioids without an effect on other facets like euphoria or constipation. [n =1]
• Turmeric primarily increases the sedative effects of opioids without changing much of anything else. [n=1]
• Anti-histamine anti-cholinergic drugs (such as diphenhydramine) potentiate the sedative and analgesic effects, but leave constipation and euphoria the same. They can increase restlessness. [pattern]

Drug Combinations

In addition to all of what was said in Making Amazing Recreational Drug Cocktails:

• DXM does not mix well with a bunch of things: 2C drugs [n>1], noopept [n=1], tianeptine [n=1], phenibut [n=1], ethyl alcohol [pattern], most nootropics. [n=1]
  • This seems to be especially bad for high-bodyload 2Cs as described above. [n>1]
• Vaporizing DMT while on ketamine “slows down” and in some cases “freezes” some aspects of the hallucinations of DMT, allowing you to inspect them more closely. It also prolongs the DMT experience for a good 3 to 5 minutes. [n=3]
• Taking 30mg of MDMA and 30μg LSD at the same time, followed by 10mg 2C-B four hours later, gives rise to a very positive synergy that allows you to maintain easy executive function while having trippy thoughts and a very high hedonic tone. It’s a smart and psychologically safe state. The combo has very mild hungover effects relative to how great it feels. [n=4]

Nootropics

• Coluracetam is surprisingly psychedelic. [n=5]
• Mixing coluracetam and weed gives rise to a mild LSD-like mindspace. [n=4]
• Rhodiola Rosea has a distinctly “dopaminergic quality”, which is rare among nootropics other than L-tyrosine. [n=3]
• Most racetams (piracetam, oxiracetam, aniracetam, etc.) successfully mask the verbal impairment (both comprehension and execution) caused by weed and/or alcohol (up to a point!). [pattern]
• Agmatine (500mg) significantly blunts the intensity of orgasm. [n=1]
• Agmatine (500mg) can be used as a replacement for NSAIDs like aspirin and ibuprofen for mild to moderate pains and aches. [n=1]

Surprising Analgesia

• Microdosing LSD (5 to 20μg) can substantially reduce the pain of very bad premenstrual syndrome (PMS). [pattern]
• Microdosing LSD can also reduce the pain associated with shingles. [1<n]