** Tolerance and Withdrawl 

	Tolerance develops rapidly to LSD, mescaline, and psilocybin, and there
is cross tolerance between them.  Cross tolerance is not exhibited between
these agents and dimethyltryptamine (DMT); and little is known about the 
development of tolerance to DOM (STP).  There are no serious withdrawl 
symptoms.

** Adverse Effects

	CHROMOSOME DAMAGE.  One of the major concerns about LSD stems from a 1967
paper by Cohen et al. (29) that suggested that LSD damages chromosomes.  Cells
with damaged chromosomes are potentially dangerous to their bearer, because 
they may establish cancerous cell lines, and are dangerous to unborn children,
because chromosomes carry the genetic message across generations.
	Dishotsky et al. (36) reviewed the results of 68 studies published between
1967 and 1970, that were concerned with the possibility of LSD-induced 
chromosome damage.  The highlights of their paper are summarized and discussed
below, but without the original references.
	The study by Cohen et al., and several studies which followed it, involved
the addition of LSD to cell cultures.  There are problems with this approach.
First, the process of culturing cells stimulates them to enter a reproductive
phase which is abnormal for them.  Second, cells in tests tubes are extremely
susceptible to chromosome breakage; aspirin, caffeine, water, and changes in
temperature or oxygen pressure are some of the many agents which induce 
breakage of the same order of magnitude as LSD.  Third, the type of breakage
produced by LSD is different from that caused by known mutagenic or 
carcinogenic agents.  Fourth, intact organisms have evolved metabolic and 
excretory systems to eliminate harmful substances, but these detoxification
mechanisms are not available to cells in test tubes.  Thus, cells have 
typically been exposed to very high doses for prolonged periods of time.
	Only four studies investigated chromosome breakage rates in humans before
and after exposure to LSD.  Only one of the studies was positive.  Several
studies reported higher breakage rates in users than in nonusers but, as has
already been discussed ad nauseum, such studies do not allow for causal
interpretation.  Some unknown factor(s), such as serious childhood illness,
may predispose people to chromosome damage ant to take LSD (see p. 176). One
obvious factor is that LSD users are likely to use many other drugs as well.
An additional problem is that breakage rates have been measured in white 
blood cells rather than in reproductive cells.
	Dishotsky et al. pointed out that chromosome damage was much more likely
to occur in users of illicit LSD than in volunteers administered known 
quantities of pure LSD in laboratories.  The probable explanation is that 
illicit LSD contains substantial quantities of adulterants (85 and below), and
these may cause breakage.  In several cases, breakage rates returned to the
normal range withing months of the last dose.
	As is so disturbingly often the case, the research may tell more about
bias in science than about LSD and chromosome damage.  Investigators who
reported more than one study tended to report the same findings in each.  
Negative findings may have resulted from small sample size or insensitive
testing procedures; for even if LSD affects chromosomes, the effects will not
show up unless tested with proper experimental procedures.  There is evidence
that the negative studies used too few subjects; thus, although only five of
fifteen studies yielded statistically significant results,*  LSD users had
nonsignificant but elevated breakage rates in 10 of the studies.

* Statistical significance refers to the probability that observed differences
  between two or more groups are due to chance factors.  Scientists 
  conventionally accept research as being statistically significant if the
  likelihood that differences are due to chance is less than 1 in 20.  If too
  few subjects are used, the results will not be statistically significant,
  no matter how strong the drug effect (just as , if a two-headed coin is 
  flipped only four times, the flipper would not be able to conclude on 
  statistical grounds that the coin is biased).  Conversely, if huge numbers
  of subjects are used, even trivial differences will attain statistical 
  significance (which, remember, means only "not due to chance"), but such
  results may have little scientific significance.
  
	There have been studies since the Dishotsky et al. paper.  In general,
these show no effect of LSD on chromosomes (42, 81, 111, 122).

ACUTE PANIC REACTIONS.  Not all drug experiences turn out as anticipated.  
Acute panic reactions, depression, paranoia, and psychotic episodes occur
with sufficient frequency to make the phrase "bad trip" and important part of
the lexicon of the drug culture.  Any potentially enjoyable event may prove to
be a disappointment, as when rainy weather spoils a picnic.  But the special
quality of drug-induced bad trips is that they cannot easily be terminated.
Cohen (31) reported that one of 2500 patients taking LSD during psychotherapy
committed suicide; and 0.02% of normal subjects who took LSD experimentally
experienced psychotic reactions of greater than 24 hours in duration.  Louria
(82) used the suicide as reason for condemning the therapeutic use of LSD, a
position that ignores the possibility that the suicide rate of patients in 
therapy and not given LSD may be higher than one in 2500.

FLASHBACKS.  Flashbacks are sudden and unexpected recurrences of aspects of an
earlier drug experience.  In a study of 2256 Army enlisted men, 23% reported
flashbacks from LSD (5% from amphetamine, 1% from marijuana) (132).  
Flashbacks have not been shown to be dangerous and, in fact, are often self-
induced.  Matefy et al. (87) quoted one user: "I just call it talking yourself
into a flashback.....It's like getting high all over again."

PROLONGED PSYCHOTIC REACTIONS.  Pradhan and Hollister (103) stated that fewer
than 1 per 1000 experimental LSD subjects, and fewer than 2 per 1000 patients
who ingest LSD, suffer psychotic reactions lasting longer than 48 hours.  
Approximately two-thirds of those who do suffer such reactions present a 
history of psychopathology prior to drug use (11).  LSD is often taken in a
last-ditch effort to solve and impending crisis which has proven refractory
to other attempts at solution (46).  If the drug does not help, symptoms may
worsen, but not because of the LSD.  The data do not justify arguments that
LSD is extremely dangerous "because of its capability to induce attempted or
completed homicide, attempted suicides, or even prolonged psychosis" (82, p.
254).

CEREBRAL DEFICIT.  Some authors have reported permanent cerebral deficit in
LSD users.  Others, however, have disputed the findings (1, 144).  In any 
event, there are no relevant experimental studies, but only comparisons of
users with nonusers.

** Benefitial Effects

Many users of LSD wax lyrical about its ability to promote insights into 
everyday problems, to enhance creativity, and to provide mystical and 
religious experiences.  These claims are evaluated in appropriate chapters.


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