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LSD's secondary effects normally last from fifty-two to seventy-five hours,[2] though as Sandoz's prospectus for "Delysid" warned, "intermittent disturbances of affect may occasionally persist for several days."[3] Contrary to early reports and common belief, LSD effects do not last longer than significant levels of the drug in the blood. Aghajanian and Bing[9] found LSD had an elimination half-life of 175 minutes, while, more recently, Papac and Foltz[10] reported that 1 µg/kg oral LSD given to a single male volunteer had an apparent plasma half-life of 5.1 hours, with a peak plasma concentration of 1.9 ng/mL at 3 hours post-dose. Notably, Aghajanian and Bing found that blood concentrations of LSD matched the time course of volunteers' difficulties with simple arithmetic problems.

Some reports indicate that administration of chlorpromazine (Thorazine) or similar typical antipsychotic tranquilizers will not end an LSD trip, it will rather become less intense or the side effects of the medication will immobilize and numb the patient.[11] While it also may not end an LSD trip, the best chemical treatment for a "bad trip" is an anxiolytic agent such as diazepam (Valium) or another benzodiazepine. Some have suggested that administration of niacin (nicotinic acid, vitamin B3) could be useful to end the LSD user's experience of a "bad trip".[12] The nicotinic acid in niacin as opposed to niacinamide, will produce a full body heat rash, due to widening of peripheral blood vessels. The effect is somewhat akin to a poison ivy rash. Although it is not clear to what extent the effects of LSD are reduced by this intervention, the physical effect of an itchy skin rash may itself tend to distract the user from feelings of anxiety. The rash itself is temporary and disappears within a few hours. It is not clear how effective this method would be for people having serious adverse psychological reactions.
Affinity of LSD for various receptors, averaged from data from the PDSP
Enlarge
Affinity of LSD for various receptors, averaged from data from the PDSP

LSD affects a large number of the G protein coupled receptors, including all dopamine receptor subtypes, all adrenoreceptor subtypes as well as many others. LSD binds to most serotonin receptor subtypes except for 5-HT3 and 5-HT4. However, most of these receptors are affected at too low affinity to be activated by the brain concentration of approximate 10–20 nM.[13] Recreational doses of LSD can affect 5-HT1A, 5-HT2A, 5-HT2C, 5-HT5A, 5-HT5 B and 5-HT6 The hallucinogenic effects of LSD are attributed to its strong partial agonist effects at 5-HT2A receptors as specific 5-HT2A agonist drugs are hallucinogenic and largely 5-HT2A specific antagonists block the hallucinogenic activity of LSD.[13] Exactly how this produces the drug's effects is unknown, but it is thought that it works by increasing glutamate release and hence excitation in the cortex, specifically in layers IV and V.[14] In the later stages, LSD acts through DARPP-32 - related pathways that are likely the same for multiple drugs including cocaine, amphetamine, nicotine, caffeine, PCP, ethanol and morphine.[15] A particularly compelling look at the actions of LSD was performed by Barry Jacobs recording from electrodes implanted into cat raphe nuclei.[16] Behaviorally relevant doses of LSD result in a complete blockade of action potential activity in the dorsal raphe, effectively shutting off the principal endogenous source of serotonin to the telencephalon.

[edit] Physical

Physical reactions to LSD are highly variable and may include the following: uterine contractions, hyperthermia (body temperature increase), elevated blood sugar levels, dry-mouth, goose bumps, heart-rate increase, jaw clenching, nausea, perspiration, pupil-dilation, salivation, mucus production, sleeplessness, paresthesia, euphoria or dysphoria, hyperreflexia, tremors and synesthesia. Cramps and muscle tension or soreness are also commonly reported, and this may be a result of the drug's effect on soft tissues such as the uterus

LSD was studied in the 1960s by Eric Kast as a painkiller for serious and chronic pain caused by cancer or other major trauma.[17] Even at low (sub-psychedelic) dosages, it was found to be at least as effective as traditional opiates while being much longer lasting (pain reduction lasting as long as a week after peak effects had subsided). Kast attributed this effect to a decrease in anxiety. This reported effect is being tested (though not using LSD) in an ongoing (as of 2006) study of the effects of the hallucinogen psilocybin on anxiety in terminal cancer patients.

Furthermore, LSD has been illicitly used as a treatment for cluster headaches, an uncommon but extremely painful disorder. Researcher Peter Goadsby describes the headaches as "worse than natural childbirth or even amputation without anesthetic."[18] Although the phenomenon has not been formally investigated, case reports indicate that LSD and psilocybin can reduce cluster pain and also interrupt the cluster-headache cycle, preventing future headaches from occurring. Currently existing treatments include various ergolines, among other chemicals, so LSD's efficacy may not be surprising. A dose-response study, testing the effectiveness of both LSD and psilocybin is, as of 2006, being planned at McLean Hospital. A 2006 study by McLean researchers interviewed 53 cluster-headache sufferers who treated themselves with either LSD or psilocybin, finding that a majority of the users of either drug reported beneficial effects.[19] Unlike attempts to use LSD or MDMA in psychotherapy, this research involves non-psychological effects and often sub-psychedelic dosages; therefore, it is plausible that a respected medical use of LSD will arise.[20]

[edit] Psychological

LSD's psychological effects (colloquially called a "trip") vary greatly from person to person, from one trip to another, and even as time passes during a single trip. Widely different effects emerge based on what Leary called set and setting; the "set" being the general mindset of the user, and the "setting" being the physical and social environment in which the drug's effects are experienced.

An LSD trip can have long lasting or even permanent neutral, negative, and positive psychoemotional effects. LSD experiences can range from indescribably ecstatic to extraordinarily difficult; many difficult experiences (or "bad trips") result from a panicked user feeling they are going to die, are going to stay insane forever or that he or she has been permanently severed from reality and his or her ego. If the user is in a hostile or otherwise unsettling environment, or is not mentally prepared for the powerful distortions in perception and thought that the drug causes, effects are more likely to be unpleasant.

Conversely, a comfortable environment and a relaxed, balanced and open mindset will often result in a pleasant experience. A common advice is that the user should make sure to just go with the flow of the experience and not try to fight it.

Many users experience a dissolution between themselves and the "outside world": cognitive differences between subject ("I") and object ("me", "you", "it") break down or seem absurd.[21] This unitive quality may play a role in the spiritual and religious aspects of LSD.

Some experts hypothesize that drugs such as LSD may be useful in psychotherapy, especially when the patient is unable to "unblock" repressed subconscious material through other psychetherapeutic methods,[22] and also for treating alcoholism. One study concluded, "The root of the therapeutic value of the LSD experience is its potential for producing self-acceptance and self-surrender,"[23] presumably by forcing the user to face issues and problems in that individual's psyche. Many believe that, in contrast, other drugs (such as alcohol, heroin, and cocaine) are used to escape from reality. Studies in the 1950s that used LSD to treat alcoholism professed a 50% success rate,[24] higher than estimates near 10% for Alcoholics Anonymous.[25] Some LSD studies were criticized for methodological flaws, and different groups had inconsistent results. Mangini's 1998 paper reviews this history and concludes that the efficacy of LSD in treating alcoholism remains an open question.[26]

Many notable individuals have commented publicly on their experiences with LSD. Some of these comments date from the era when it was legally available in the US and Europe for non-medical uses, and others pertain to psychiatric treatment in the 1950s and 60s. Still others describe experiences with illegal LSD, obtained for philosophic, artistic, therapeutic, spiritual, or recreational purposes.

[edit] Sensory/perception

Generally beginning within thirty to ninety minutes after ingestion and continuing for the following six to twelve hours, the user may experience anything from subtle changes in perception to overwhelming cognitive shifts.

Changes in aural and visual perception are common, ranging from mild to profound.[21][27] These sensory changes include basic "high-level" distortions such as the appearance of moving geometric patterns, new textures on objects, blurred vision, image trailing, shape suggestibility and color variations. Inanimate objects are frequently described as "breathing". Users sometimes describe experiencing new, previously-unseen colors; sights and sounds may take on greater intensity or have more of an impact. Users commonly report that the inanimate world appears to animate in an unexplained way; that is, objects that are static in three dimensions can seem to be moving relative to one or more additional spatial dimensions.[28]

Higher doses often bring about shifts at a lower cognitive level, causing an intense and fundamental reinterpretation of sensory perception, symptomatic of synesthesia.

[edit] Spiritual

LSD is considered an entheogen because it often catalyzes intense spiritual experiences where users feel they have come into contact with a greater spiritual or cosmic order. It is common for users to achieve insights into the way the mind works and some users experience permanent or long-lasting changes in their life perspective because of what they have experienced. Some users consider LSD a religious sacrament, or a powerful tool for access to the divine. Many books have been written comparing the LSD trip to the state of enlightenment of eastern philosophy.

Such experiences under the influence of LSD have been observed and documented by researchers such as Timothy Leary and Stanislav Grof. For example, Walter Pahnke conducted the Good Friday Marsh Chapel Experiment under Leary's supervision, performing a double blind experiment on the administration of psilocybin to volunteers who were students in religious graduate programs, e.g., divinity or theology.[29] That study showed that hallucinogens could reliably be used to induce mystical religious states (at least in people with a spiritual predisposition).