Title: Pathology of Drug Abuse
Date & Time: Wednesday, November 30, 2011 at 10 AM
Lecturer: The Pathology Team
No quizbank for this one
THE ILLEGAL DRUGS
I see the Truth, when I'm all stupid-eyed...
-- Nine Inch Nails, "The Perfect Drug"
There's no room here for a major treatise on recreational drug abuse, but when you start seeing patients, you'll be impressed with the problems they cause.
Uncle Sam (1994) reported that usage peaked in 1975, with 23 million users (i.e., people who'd taken a recreational drug in the previous month). Now that the public is more savvy (maybe), and people can lose their jobs if they flunk random drug tests (definitely), the count is down to maybe 11 million, but this is the hard-core.
Your lecturer has been observing the drug scene since the sixties. IN MY HONEST, CONSIDERED OPINION, THE RECREATIONAL USE OF TODAY'S ILLEGAL DRUGS HAS NOTHING TO RECOMMEND IT.
Especially, decide how much of this behavior is identity-group membership. This might explain why minority groups (racial minorities, "disenfranchised youth") usually prefer different intoxicants and/or patterns of consumption than the majority culture. Not surprisingly, cognitive-behavioral treatment for depression seems to help intractable drug-abusers (Arch. Gen. Psych. 68: 577, 2011). |
Bess and Sportin' Life: "Happy Dust" |
Some of the essential pathophysiology remains mysterious. We don't even know why pulmonary edema is usual in opiate overdoses, or why people who do street drugs tend to have a hepatic triaditis and enlarged portal lymph nodes. Talc or whatever crystalline substance was present in the injected mixture often finds its way to the portal macrophages, which may also be pigmented.
* The most interesting new work in this area, an examination of gene expression profiles in the nucleus accumbens, tends to discredit the recently-popular idea that the various addictive drugs work through a common pathway ("the addicted brain..."). See Neuropsychopharmacology 31: 2304, 2006.
* The amygdalas (brain areas that have to do with self-control) in the experienced cocaine-user afflicted with craving seem much smaller than those of normal folks (Neuron 44: 729, 2004). Cause (weak-willed in the first place / stupid enough to try cocaine) or effect (damage from cocaine) or both? We are eagerly awaiting an answer.
Likewise, the medicolegal evaluation of the deaths of drug-users is fraught with pitfalls.
Tolerance, i.e., decreasing drug effect as the dose is held constant, makes it difficult to say whether the amount that the person took could / could not have been lethal.
Illegal drugs and their metabolites are easily measured in blood and tissue after death, but post-mortem drug levels must not be over-interpreted.
Especially, drugs redistribute after death in ways that so far have baffled the best forensic scientists (J. For. Sci. 44: 10, 1999). Obviously as body proteins denature and temperature and pH change, affinities for the molecules change and drugs diffuse. Most forensic pathologists will simply tell you, "This lab result means the person did this drug."
The specificities of your screening tests may be insufficient to detect particular drugs. For example, today's "opiate screen" is likely to miss fentanyl.
And of course, the drugs that were at the scene at the time of overdose are likely to be gone by the time that the police arrive.
Terms to know:
BODY STUFFER: Someone who conceals the drug in a packet in the body before being arrested.
Both types can show up in the emergency room very, very sick (J. Tox. Clin. Tox. 42: 987, 2004; Ann. Emerg. Med. 55: 190, 2010.
 Less Than Zero |
* Centers or wooden frames are put under the arches of a bridge, to remain no longer than till the latter are consolidated, and then are thrown away or cast into the fire. Even so, sinful pleasures are the devil's scaffolding to build a habit upon; and once formed and fixed; the pleasures are sent for firewood, and hell begins in this life. |
Today, this euphoriant-anesthetic substance needs no introduction. Taken by needle, through the nasal mucosa, or smoked in heat-resistant form as "crack" (from the cracking sound made by the crystals), it's has long been major evil presence. There's a mild physiologic withdrawal syndrome. More seriously, once the drug is sampled, the psychologic craving is intense.
Even experimenting a little with cocaine, even "to help you study", is extremely dangerous. Apparently cocaine use destroys your capacity to be happy without the drug. The cocaine addict will do anything to get more of the drug.
In the 1980's, the introduction of a cheap, smokable form ("crack", from the sound of the blocks breaking as they burn in the pipe) caused a striking increase in use. According to Sci. Am. 290: 82, Feb. 2004, the use of crack dropped precipitously in the early 1990's. The author's explanation was that community leaders recognized that the danger to their communities' health was too great to accept as "politics and profits as usual", and "extra-judicial street justice" removed the crack dealers. Today's social scientists attribute the tremendous increase in crime between the late 1980's and the mid-1990's largely to the rise and fall of crack.
Cocaine kills people in at least five different ways:
Cocaine and the heart: NEJM 345: 351, 2001; Am. J. Card. 100: 1040, 2007. It is adrenergically mediated and potentiated by both ethanol and tobacco. Cocaine depletes dopamine receptors on the coronary arteries, and renders them super-sensitive to alpha-adrenergic stimuli. This is most likely the cause of the vasospasm (Am. J. Card. 86: 1054, 2000) and symptoms and signs of cardiac ischemia.
Less well-known is smoked cocaine's ability to produce damage to the pulmonary microvasculature (Chest 121: 1231, 2002). Even if the patient does not have hemoptysis, this is one cause of a lung's being full of hemosiderin-laden macrophages. Check the blood for cocaine in any young person with unexplained hemoptysis.
Remember that even though the brain rapidly develops tolerance to the euphoriant effects of the drug, the sodium channels of the heart never develop tolerance to the effects of cocaine. This triggers rhythm disturbances and death.
Pathologists look for these findings, which are typical of heavy cocaine users and to a lesser extent other stimulant users: (1) Replacement of single cardiac myocytes by fibrous tissue (probably why we get the diastolic dysfunction of the left ventricle; this is distinctive for "chronic catecholamine cardiomyopathy" of which cocaine heart is the chief example); (2) Medial hypertrophy of the small coronary resistance arteries. (For a review with photos see South Med. J. 98: 794, 2005).
Tachyarrhythmias probably result from the underlying anatomic changes in the heart, since (unlike myocardial infarction), they won't happen during the first experimenting.
Brain hemorrhages happen even if the vessels in the head are "normal": Neurology 46: 1741, 1996; brain vessel constriction can also produce stroke: JAMA 279: 376, 1998.
"Crack lung" produces a spectacular anthracosis.
* You may be told that cocaine produces a vasculitis, especially in the brain (Neurology 40: 1092, 1990). I don't know whether this is true; most cocaine users get no vasculitis from the drug. So far as I've been able to find out, there's no distinctive lesion; it may be just a rare Stevens-Johnson drug-allergy vasculitis.
Future medical examiners:
Cocaine is metabolized into benzoylecgonine (serum half life 6 hours, urine half-life 12 hours) and ecgonine methyl ester (serum half-life 4 hours); both degrade into ecgonine which is stable indefinitely. If there is also alcohol on board, about 10% of the cocaine will be turned into cocaethylene, a psychoactive compound with a half-life of 3 hours.
Watch for post-mortem studies on brain receptors in cocaine addicts, to demonstrate and understand tolerance.
Crack lung
Lung pathology series
Dr. Warnock's Collection
The famous perforation of the nasal septum is simply an ischemic infarct from vasoconstriction. Cocaine can also kill unborn children by abruption of the placenta or direct toxicity to the fetus (For. Sci. Int. 47: 181, 1990; still clearly true Am. J. Ob. Gyn. 204: 340, 2011), or make babies small and/or premature. Today's "crack babies" need no description (ask a pediatrician, or see Pediatrics 97: 851, 1996; these babies are significantly smaller Pediatrics 101: 229, 1998; Although the most dire predictions have not held up and non-crack-exposed underclass kids also have special problems (Pediatrics 98: 938, 1996; J. Ped. 132: 291, 1998), the "crack babies" do seem to have been damaged permanently by the drug (Pediatrics 120: e1017, 2007).
* One future hope is a vaccine, i.e., a cocaine analogue that is immunogenic, producing antibodies that bind cocaine and prevent its having an effect. Hope it works. See Nature 378: 727, 1995; Proc. Nat. Acad. Sci. 98: 1988, 2001. Vaccines are also "under development" for nicotine, methamphetamine, phencyclidine, etc., etc., but after a decade there's been nothing really promising (Curr. Psych. Rep. 9: 381, 2007).
EXCITED DELIRIUM is a curious phenomenon in which a person (most often on cocaine or amphetamines, though the blood levels need not be high and it's seen sometimes without drugs on board) requires physical restraint, then stops struggling and shows labored / agonal breathing and immediately goes into cardiopulmonary arrest. The syndrome is defined to be each of these in succession: (1) hyperthermia, (2) delirium, (3) respiratory arrest; (4) death. Nobody really knows the mechanism (Am. J. Emerg. Med. 19: 187, 2001).
The phenomenon is so familiar to forensic pathologists and to the police that I have no serious doubt that it's real. The autopsy molecular signature is now reported to be elevated HSPA1B and much-diminished dopamine transporter (For. Sci. Int. 190: e13, 2009).
Of course, excited delirium generates a lot of bogus "police brutality" lawsuits. Update on excited delirium deaths in custody, viewed with 20/20 hindsight back to 1939: AMFJP 30: 1, 2009. Of course, some of these people die WITHOUT being taken by police, in the way described above (J. Anal. Tox. 33: 557, 2009). Your lecturer believes that excited delirium, rather than "police brutality", is the usual mechanism of death when someone who the police have hog-tied dies suddenly (Am. J. For. Med. Path. 31: 107, 2010).
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DOWNERS (barbiturates, others)
Overdoses can be fatal, especially if you've had a drink. (NOTE: Your lecturer doesn't believe that it's common for people to "forgetfully" take the rest of the bottle of sleepers while groggy from taking just one.) For big-time abusers, there's a physical tolerance and withdrawal syndrome (excitement, seizures) that can kill you. Remember skin blisters in people in "barb" coma; nobody knows why they happen.
Gamma-hydroxybutyrate (gamma hydroxyburytic acid), gamma-butyrolactone, and 1,4-butanediol (the latter is an industrial solvent, yuck) are popular yuppie downers. Gamma-hydroxybutyrate mimics GABA, the inhibitory neurotransmitter, and crosses the blood-brain barrier easily. Again, there's a physical dependence and the risk of acute toxic death (NEJM 344: 87, 2001).
Even old-fashioned sedatives such as chloral hydrate still kill people.
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The benzodiazepines ("Valium", etc.) are amnesic drugs. You won't learn well while you're taking the stuff "for test anxiety" or anything else. Today's "more sophisticated" exam-takers are choosing propranolol, a drug with effects on the heart that are not always salutary. Put that stuff away, too.
* Even the anesthetic propofol is now being used by people seeking a relaxant; it turns out tobe addictive (Clin. Tox. 48: 165, 2010).
UPPERS
The amphetamines ("speed"; most-used right now is methamphetamine; update Mayo Clin. Proc. 81: 77, 2006) are rough on the heart (sudden death is famous; also "meth cardiomyopathy" Am. J. Med. 120: 165, 2007; disturbingly comon Am. J. Card. 102: 1216, 2008), brain, and kidneys, and may incline their users to do foolish, hurtful things. However, sudden deaths from these substances are uncommon, and tend to mimic cocaine's anatomic pathology.
Compared with the other drugs of abuse (except ethanol), "meth" is much more likely to lead to death or serious injury by making its users violent and reckless. Of course, we are in the midst of a "meth" epidemic, and folks in the emergency room in San Diego are more likely to be on "meth" than even marijuana (J. Trauma 63: 531, 2007).
Probably no one was surprised to learn that cocaine and methamphetamine users get horny and do reckless sexual things (Am. J. Psych. 164: 157, 2007).
The famously-bad tooth decay and fractured teeth seen in the methamphetamine user is caused by a combination of xerostomia, the noxious smoke ("crystal meth" / "ice"), bruxism, and a craving for sugar (Am. J. Health-Syst. Pharm 63: 2078, 2006; Gen. Dent. 54: 125, 2006). It's hard to show in the lab, but your lecturer believes that vasoconstriction from the drug probably infarcts the mouth tissues.
Like "crack babies", "meth babies" born to women who did methamphetamine are much smaller than their counterparts. We await follow-up (Pediatrics 118: 1149, 2006; confirmed Ob. Gyn. 116: 330, 2010; J. Ped. 157: 337, 2010).
Phencyclidine's pathology is being worked out. It's been a challenge as specific lesions haven't been found, and it's hard to know who's been using. The NIH finally starts looking at folks' "true addiction history" by hair samples, but this isn't feasable for your limited-budget medical examiner (Addiction Biology 13: 105, 2008).
Mephedrone is an amphetamine available as tablets; it famously causes bruxism (tooth grinding); it's resurfaced and is now being made illegal. (For. Sci. Int. 206: e93, 2011).
3,4-methylenedioxymethamphetamine ("Ecstasy" / MDMA) is a familiar yuppie drug whose problems are now being studied intensively.
A curious effect is hyponatremia, as the drug seemes to cause both inappropriate secretion of ADH and inappropriate water drinking. This is now a robust finding (Am. J. Med. Sci. 326, 89, 2003; Ann. Emerg. Med. 49: 164, 2007), and can be lethal.
Use of MDMA is common, deaths from MDMA are rare, and they usually resemble other amphetamine-type deaths (Legal Med. 9 185, 2007).
"Bath salts" (* methylenediosypyrovalerone, MDPV; unrelated to any real hygneie product) appeared in early 2011 as a legal stimulant, skirting laws. The can produce extreme sympathetic stimualtion and craziness (NEJM 365: 967, 2011).
* In 2011, synthetic chemicals were marketed in stores as "bath salts", supposedly to be put in your bathwater rather than be consumed as the amphetaminelike drugs that street people knew they were. They killed a few people, resulted in quite a few speed-like emergency-room visits, and are now being made illegal (Clin. Tox. 49: 499, 2011; MMWR 60: 624, 2011; NEJM 365: 967, 2011). Compare New Zealand's "party pills" (piperazines): Clin. Tox. 49: 131, 2011.
* Not really uppers: KETAMINE has caused surprisingly few deaths in recreational users, who are likely to be medical types. See Int. J. Leg. Med. 116: 113, 2002.
* Not really uppers: LSD and mescaline are seldom encountered today (which is good); there is no known anatomic pathology (Clin. Tox. 48: 350, 2010.)
{07615} tattoo on public-spirited person
Montana Meth Project
Drug-ed ads.
Enjoy.
OPIATES
Heroin, morphine, and meperidine are usually taken by needle (intravenous or skin-popping; there are ways of inhaling "the dragon" heroin). Codeine, hydrocodone, and oxycodone are taken orally. Your lecturer is not impressed with the adverse personality or health consequences of opiate use itself (well, it's constipating and bad for the libido). However, the stuff is addictive, expensive, and illegal (which causes some of the problems) and overdose is very lethal. Stories from eyewitnesses describe collapse, gurgling, and a massive gush of foam from the mouth. |
 Poppies are Also Flowers |
 | Unlike cocaine, heroin is not known to have any direct tissue toxicities. There are maybe 4000 deaths from heroin overdose in the US each year. Those dying of heroin overdose either (1) stopped breathing from medullary depression, or (2) got pulmonary edema (nobody knows why opiates can do this, but it's likely that it's neurally-mediated, because of tolerance and because brain injury itself can produce similar edema). Of course, there are plenty of heroin-related deaths due to lifestyle and/or unsanitary injection practices. |
It's commonplace for an "accidental" overdose to have been preceded by a critical life-event, and many of these "unfortunate tragic accidents" are probably suicides (Forens. Sci. Int. 62: 129, 1993).
* Confusingly, there is an illness seen only in people who snort cooked heroin, and that much be due to some other poison generated in this way. It looks clinically and anatomically like prion disease, but some patients recover; it's called "heroin spongiform encephalopathy" and is recognizable now on MRI scans: For. Sci. Int. 113: 435, 2000.
Social scientists tell us that heroin was responsible for the upsurge of crime, especially robberies, from the mid-1960's to the mid-1970's. Methadone maintenance as a readily-available treatment proved a great help (thanks very much for that one, Mr. Nixon).
Methadone / suboxone maintenance keeps drug addiction, which is a relapsing problem, under partial control with great savings to society. There are about 100,000 people on methadone maintenance in the US, and only about 500 deaths per year from overdosing. Most deaths result from increasing the initial dose too rapidly.
You'll review the various molecules in "Pharm". Don't try too hard to interpret a post-mortem morphine level, either to decide whether "it's enough to kill the person", or how much of the drug was taken. Tolerance varies tremendously, and attempts to second-guess tolerance by high-tech assays of brain receptors have been non-helpful: For. Sci. Int. 113: 423, 2000. During life, 98% of a dose of opiate is in the tissues; as the body decomposes, much of it will return to the bloodstream. Review J. For. Sci. 46: 1138, 2001. Redistribution is less of a problem than for other drugs: J. For. Sci. 45: 843, 2000.
* Don't forget to look for pupa cases from the maggots that fed on the body. Morphine can be analyzed from here: For. Sci. Int. 120: 127, 2001.
"Big Robbins's" statement that a third of heroin addicts had diluted their drug with water from the
toilet comes as no surprise to this physician. Heroin may be cut with Baby's talcum powder (stays in
the lungs forever), quinine (rough on the heart), or whatever else is handy (who knows?) Heroin
addicts seldom use sterile technique, and abscesses and endocarditis (notably on the tricuspid valve,
notably staphylococcal
)
are commonplace, as is the bad retrovirus. "Heroin nephropathy" is usually
FSGS (also amyloidosis A, from the abscesses.)
It's worth remembering that tolerance to opiates is lost VERY fast. One common scenario is a fatal overdose after a 2-3 day stay in jail; the addict simply took the customary dose and died as a result (for example, the death of Sid Vicious). Savvy medical examiners are now estimating these people's tolerance history using hair samples.
Ultra-rapid detoxification, which ends the addiction during a few hours of artifical sleep and naloxone treatment, has been available since the 1990's and the military (i.e., reality-based) now uses it for burn victims (J. Trauma 71(1S): S-114, 2011).
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Ask a forensic pathologist to show you needle marks ("tracks"). These are scars, often pigmented (carbon, hemosiderin), overlying veins and often arranged in a line (savvy dopesters start distal). One reason addicts get tattoos is to make it harder to see their injection sites. "Skin poppers" are often covered with old craters.
among skin-poppers whose heroin was
mixed with dirt: Science 288: 1941, 2000; Lancet 356:
1574, 2000.
{08170} heroin tracks
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People who inject "Ritalin", "Talwin" or methadone from powdered tablets are also certain to get interesting stuff in their lungs. Talcum powder and pill-fillers both produce little granulomas, which can eventually cause fatal cor pulmonale.
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* Buprenorphine implants for the treatment of opiate dependence: JAMA 304: 1576, 2010.
The management of patients with chronic pain is only now receiving the recognition it deserves from the medical profession, and is still restricted by laws that don't make sense (a fact that is finally getting media attention). Heroin may perhaps have some use in the management of chronic pain, but the discussion is totally dominated by ideological concerns. Today, however, most users chose heroin not for a physical analgesic but as a powerful anesthetic against deplorable living conditions. It works (and this would lead me to ask why so many people feel they need it -- perhaps the cause is having to live around other substance-abusers, criminals, and mean people), but the problems only begin with impotence, constipation, and infections.
* For the not-pretty picture of both TB and morphine addiction in the pre-illegal era, read or see
Eugene O'Neill's autobiographical "Long Day's Journey into Night".
{07062} talc in heroin-abuser's lung
Baudelaire, Toulouse-Lautrec, Van Gogh, and Rimbaud were devotees of the drug, which raises the question (for me anyway) whether their devotion to the drug was the cause of, or the result of, their particular outlooks on life. The movie "Moulin Rouge" (2001) celebrates the hallucinations generated by absinthe. A Jayhawk argues that VanGogh's psychosis was at least exacerbated by his absinthe: JAMA 260: 3042, 1988; more by this author on absinthe: Sci. Am. 260(6): 112, June 1989.
The special ingredient that produced the weird intoxication is supposedly thujone. If you believed everything you read about this, you'd be reading uncritically. Despite its molecular resemblance to the active ingredient of marijuana, it doesn't work on the cannabinoid receptors. More credible is work showing that it acts on the GABA type A receptors (Proc. Nat. Acad. Sci. 97: 3826 & 4417, 2000). This suggests excitotoxicity as the cause of the permanent brain damage.
* The sad story of a man who drank wormwood obtained via the internet: NEJM 337: 827, 1997.
| After the first glass you see things as you wish they were. After the second, you see them as they are not. Finally, you see things as they really are, and that is the most horrible sight in the world. |
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What did the two stoners say to each other when they finally ran out of marijuana? |  |
The familiar weed, which archeologists tell us goes back at least to the 6th millennium BC, binds to particular receptors in the brain, as do most other drugs. The active agent is delta-9-tetrahydrocannabinol. Ask a neuropharmacologist about the "cannabinoid receptors", and the endogenous cannabinoids, notably N-arachidonoylethanolamine (charmingly named "anandamide", ananda being Sanskrit for "bliss.")
* Formerly the hemp plant was cultivated widely in the US for
rope and canvas (same word as "cannabis").
People seeking rational explanations for our curious marijuana
laws have suspected the political influence of
the cotton industry ("King Cotton"; canvas clothes are less
comfortable but more durable) and of course the big liquor companies.
Or (and this seems right to me) this is just another example
of "the law of alien poisons", i.e., that every dominant culture abhors
the mind-altering substances preferred by its minority groups, and cannabis
was primarily used by Hispanics who called it "Mary Jane" (Substance Use and Misuse 37: 853, 2002: from Nova Southeastern COM).
Something on this history of the international ban on marijuana, with a reminder
that it was largely driven by a disinformation campaign by a single US politician:
Lancet 313: 344, 2004.
The "medical marijuana" laws are inadequate to
provide the obvious benefits the drug offers (NEJM 362: 1453, 2010);
but even the Bush administration (October 2009) reversed itself and stopped
sending the Feds after people using the drug in accordance with their
states' medical marijuana laws.
There is a mild withdrawal syndrome seen only in heavy users (i.e., four or more joints per day) that lasts less than a month, with the ex-stoner losing weight, sleeping fitfully, and being crabbier ("increased aggression" shows only on lab tests that seem to measure irritability): Am. J. Psych. 161: 1967, 2007.
In one long-term study, stoners who weren't already crazy were somewhat more likely to go crazy ("exhibit psychotic symptoms") than non-stoners -- cause and effect, or effect and cause? You decide BMJ 342: d738, 2011).
Right or wrong, the government crusade against marijuana has long been a part of "politics as usual". Marijuana smoking was a "political" act during the 1960's, when the government's several "credibility gaps" were obvious and many people were given absurdly long prison terms simply for possessing a joint or two. It seemed to make its known users unmotivated, and your lecturer suspects this means it causes subtle brain damage that may or may not be reversible. If the latter is really true, it has resisted scientific demonstration.
* Ironically, at the same time that
marijuana was the drug of choice for the 1960's, mostly anti-Vietnam-war
"counterculture",
it was also the drug preferred by front-line troops during the war,
who preferred it to alcohol since they wanted to be able to fight effectively in case of surprise attack.
* Government and government-promoted (D.A.R.E.) material for young people
about
the supposed risks of marijuana includes obvious, preposterous untruths.
For example:
* Of course, this undermines the credibility of warnings about dangers
of heroin, cocaine, methamphetamine, and the other genuinely-life-threatening drugs.
In the US, politics-as-usual includes the maintenance of an illegal drug culture
among the poor and the stupid, with marijuana as the gateway drug.
Draw your own conclusion.
It is known that marijuana undermines the immune system so it is likely
that in another 20 years, if use continues to escalate, the death toll
from side effects of long-term marijuana use will equal those of longer-term
tobacco use.
Sandra
S. Bennett, D.A.R.E. website
Retrieved July 21, 2007
Your lecturer makes yearly medline searches that always reveal exactly nothing plausible about serious health consequences of marijuana smoking (beyond an ultra-rare, Buerger-like "cannabis arteritis" (Br. J. Derm. 152: 166, 2005; J. Am. Acad. Derm. 58(5S1): S65, 2008; the Germans reviewed the data and decided there was no such thing Vasa 39: 43, 2010). NOR CAN THIS WRITER IMAGINE HOW THE NEUROLOGIC "AMOTIVATIONAL" SYNDROME (if it is real) COULD BE CLEARLY DISTINGUISHED FROM THE APATHY AND ENNUI OF SPOILED MODERN-DAY U.S. KIDS. This includes the effort in JAMA 287: 1123, 2002, in which Aussies who smoke weed daily for decades have progressive impairment of memory and attention (thanks for trying). Even the Canadians, not known for liberalism, found that the well-known stupidity (i.e., lowered IQ) of stoners is measurable only in those smoking five or more joints weekly, and that looking at past users, "we conclude that marijuana does not have a long-term negative impact on global intelligence" (CMAJ 166: 887, 2002). A mega-study involving imaging of the brain of young teens found smaller brains in those exposed to alcohol, to cocaine, and to tobacco -- but there was no demonstrable effect from marijuana (Pediatrics 121: 741, 2008). In 1999, Bethesda funded a huge study on medical marijuana; it is reviewed in Arch. Gen. Psych. 57: 547, 2000 -- after a lot of hearings and calls for more research, the one solid recommendation was a metered inhaler rather than just letting the patient smoke the weed as a joint. (No, this doesn't make sense to me, either). Studies showcasing the common-sense idea that marijuana helps with chronic painful illnesses continue to be published in major journals (Neuro. 68: 515, 2007 -- the patients are now allowed to smoke the stuff.) The 2002 claim that cannabis smoking causes 30,000 deaths in Great Britain seems built on faulty assumptions -- you decide: Br. Med. J. 327: 165, 2003. Contrast this with a study from JAMA 299: 525, 2008 indicating more periodontal disease in stoners independent of tobacco use -- without considering that perhaps stoners do not brush-floss their teeth so often as non-stoners. How frankly nonsensical the world marijuana laws are: Lancet 363: 344, 2004 (again, not a bastion of liberalism).
You should not smoke cannabis and then drive a car. This was "prove-able" only after blood assays for marijuana smoking became available. See Lancet, April 24, 1976, page 884. A group of Canadian academicians conducted a phone survey asking (1) "Do you drive your car when you are high on marijuana?" and (2) "How many fender-benders have you had?" They discovered that people who drive stoned average twice as many wrecks (no surprise: Traffic Injury Prevention 11: 115, 2010).
* In 1997, a team in Italy noticed that cannabis and heroin both activated mesolimbic dopamine transmission by a common receptor mechanism. The subsequent claim that this suggested marijuana was addictive met with guffaws; it seems to me that it simply reflects the fact that both drugs make people happy while they're high (Science 276: 1967, 1997; this would not be worth mentioning except that it got published, somehow, in this distinguished journal and you may hear about it.) Nobody seems to have trouble stopping marijuana smoking.
Of course, marijuana use results in very few domestic-violence calls. Contrast alcohol. It's also very widely reported to be easily the best way to overcome the dreadful subjective side effects of cancer chemotherapy. This is intensely politicized (your chemotherapy patients will try it themselves, and probably not tell you). Even Canada, not known for radical social politics, legalized medical marijuana in 2001.
Your lecturer hasn't seen anyone physically sick or dead from marijuana, and believes that claims of grave health threats, birth defects, and so forth are simply disinformation. Nor has your lecturer heard of dreadful harm from countries where marijuana is available legally at convenience stores. Even the new edition of "Big Robbins" trimmed its warnings against marijuana down to concern about smoke damaging the lungs and being stoned making your thinking fuzzy. JAMA 287: 1172, 2002 confirms what everybody knows -- even 17 hours after getting zonked on marijuana, your head's not quite clear. The JAMA editors, not known for being left-wing, also pointed out that most current work does NOT really support the idea that marijuana causes long-term brain damage, and that it's also impossible to tell in any case whether people who smoke a lot of dope are stupider to begin with. (You think?) Science takes a back seat to politics, and truth be told, almost nobody's doing meaningful scientific work with marijuana use itself today. This is a shame, since (for good or ill) the drug is a well-established part of U.S. culture, and (because it is illegal) might be purchased from the same kind of folks as the much more dangerous drugs (i.e., kids learn how to buy from drug dealers). Plus, the brain systems on which it works are evidently quite important (Nat. Med. 9: 1227, 2003). A review of adverse health effects of non-medical cannabis use (Lancet 374: 1383, 2009) emphasized the lack of any real science. The one strong recommendation is to not drive a car when stoned.
* Synthetic cannabinoids ("Spice herbal incense") that actually do work on the cannabinoid receptors (Eur. J. Pharm. 659: 139, 2011) are now being made illegal (For. Sci. Int. 208: 47, 2011).
* Why do you THINK they call it "dope"? -- Ed
THE INHALANTS ("glue sniffing", etc.)
Some people have fun inhaling solvents (acetone, ethyl acetate), gasoline, isobutane (cigaret lighter fluid Int. J. Leg. Med. 120: 168, 2006); isobutyl-, amyl- and butyl-nitrites ("pig pokers", etc.), nitrous oxide ("Whippets", from aerosolized whipped cream cans; a yuppie favorite), toluene (airplane glue), and fluorocarbon (J. For. Sci. 38: 477, 1993) propellants.
Solvents probably act (like general anesthetics) by solubilizing the lipid in nervous tissue and acting on the same proteins as anesthetics do. Use of some of these drugs can be bad for the heart (sensitizes to rhythm disturbances), kidney, and brain. Intoxicated people can die of aspiration or asphyxia.
Nitrous oxide users are prone to develop a peripheral neuropathy and megaloblastic anemia.
* My favorite article from 2007 was the account of the autopsy of a sniffer of toluene from paint. Granules of aerosolized paint in the lungs were magnificently demonstrated on electron microscopy (For. Sci. Int. 171: 118, 2007).
There's no time or reason to dwell on the arcane, political-legal subject of testing for drugs of abuse.
Worth knowing: Heroin is metabolized to morphine, and cocaine to benzoylecgonine and ecgonine methyl ester. You measure these.
RULE: If there's to be a legal impact of your findings, you must confirm all positives using a test based on a different chemical principle.
* It is possible to test meconium to see whether Mom has used drugs during pregnancy. Early work (J. Ped. 122: 152, 1993) suggested this might become routine, but understandably it's primariy a research tool, though it has finally come into widespread use (Pediatrics 118: 1149, 2006; Arch. Dis. Child F&N 91: F291, 2006; Clin. Chim. Acta 366: 101, 2006; For. Sci. Int. 153: 59, 2005).
One fact that needs to be understood by a society considering de-criminalization of marijuana is the fact that it remains detectable in the user's urine longer than more dangerous drugs. People who want to party on Friday night but will lose thier jobs if they are found "drug-positive" on a random urine check on Monday know this, and are more likely to use meth or cocaine instead.
* For more on the "war on drugs" and facts that may
guide your thinking in an area where there are no easy answers,
see the online version of these notes.
Lacerations and incisions
Anna Nicole Smith
Heroin-cocaine death
Crystals in the lungs of drug abusers