Plants and psychopharmacology
The Pharmacognosy Focus Group of the Academy of Pharmaceutical
Sciences hosted a symposium on “Plants and psychopharmacology” on
16 September. The session, chaired by Professor Peter Houghton of the
pharmacognosy research group, King’s College London, included presentations
on both preclinical and clinical research
Herbal hype about hypericum?
The question “Is there too much hype
about hypericum?” was
addressed by Dr Jo Barnes of the centre for pharmacognosy and phytotherapy,
School of Pharmacy, University of London. Her presentation gave an overview
of St John’s wort (Hypericum perforatum, hypericum), including
an update on clinical research investigating the efficacy of herbal medicinal
products containing extracts of St John’s wort herb in the treatment
of depression.
There is a large market for St John’s wort products in the United
Kingdom, the United States and other developed countries. In market research
carried out in 2000 on “alternative medicines and treatments” used
by UK adults, 6 per cent reported that they had used St John’s
wort at some time. A small survey of adult users of St John’s wort
in the US found that common reasons for its use in preference to conventional
antidepressants were the perception that it is safer and is more accessible.
Major constituents of St John’s wort herb include hypericin and
hyperforin. Hyperforin is thought to be one of the major compounds responsible
for the antidepressant effect of St John’s wort, but other compounds
and groups of compounds, such as the flavonoid constituents, may also
be important. The precise mechanism of St John’s wort’s antidepressant
activity is also not yet known. Inhibition of synaptosomal uptake of
several neurotransmitters, including serotonin, dopamine and noradrenaline
(norepinephrine), has been documented.
Dr Barnes discussed a Cochrane meta-analysis of randomised clinical trials
of various St John’s wort preparations involving patients with
mild to moderately severe depression. This showed that, overall, treatment
with St John’s wort herb extracts was significantly superior to
placebo. Since there are marked differences between St John’s wort
products produced by different manufacturers, the authors also undertook
smaller meta-analyses for two specific manufacturers’ products
(LI-160, Lichtwer Pharma; Psychotonin, Steigerwald) which had each been
tested in several randomised controlled trials. The smaller meta-analyses
showed that each of the two products was significantly better than placebo
in treating symptoms of mild to moderately severe depressive disorders.
St John’s wort has received much attention in the past two years
or so because of its pharmacokinetic and pharmacodynamic interactions
with certain prescription medicines, including warfarin, theophylline
and ciclosporin. The Committee on Safety of Medicines and the Medicines
and Healthcare products Regulatory Agency have received at least 40 such
reports via the yellow card scheme for adverse drug reaction reporting
since October 1996. Reports of suspected interactions with other drugs,
such as irinotecan, are emerging. Pharmacists should consider the possibility
of concurrent use of St John’s wort products and prescription medicines,
be vigilant to potential interactions, and report suspected interactions
using the yellow card scheme.
The pharmacist’s role should also extend to considering the place
of St John’s wort in the treatment of depression, although standard
pharmaceutical reference texts give little guidance on this at present.
A recent issue of the Drug and Therapeutics Bulletin stated that antidepressant
drugs (ie, conventional agents) may not be optimal treatment for mild
depression in primary care.
In Dr Barnes’ view, research effort directed at exploring the efficacy
of St John’s wort herb extract in this setting is warranted, since
most clinical trials to date have been carried out in the hospital setting.
Is soya good for your brain?
Dr David Hartley, psychopharmacology research unit, King’s College
London, said that there has been increasing interest in the role in human
health of soya and isoflavones found in soya. Areas of interest include
the prevention of breast and prostate cancer, cardiovascular disease,
osteoporosis and menopausal symptoms.
In his presentation, Dr Hartley discussed several preliminary clinical
studies carried out by his group exploring the cognitive effects of soya.
One study had compared the effects of a low- and high-soya diet (equivalent
to 0.5 and 100mg isoflavones daily, respectively) on measures of memory
in healthy students. After 10 weeks, improvements in non-verbal memory
tests and in mental flexibility (eg, ability to learn a new task) were
observed in the high-soya diet group, compared with the low-soya diet
group. In another small study (n=33) involving postmenopausal women who
received a soya isoflavone supplement, Solgen, one capsule twice daily
(60mg total isoflavones equivalents daily) or placebo for 12 weeks, participants
in the soya group showed significantly greater improvements in picture
recall, in a sustained attention task and in a planning task, compared
with the placebo group.
Asked about a possible mechanism of action for the cognitive effects
of soya, Dr Hartley said this is unclear. Isoflavones are known to bind
with a greater affinity to oestrogen receptors of the beta rather than
alpha subtype, and receptors of the beta subtype are abundant in the
cerebral cortex and hippocampus. However, this and the cognitive effects
of soya isoflavones need further investigation.
Testing for the cognitive effects of ginseng
Ginseng is “probably the single most widely taken herbal product
in the world”, according to Dr David Kennedy, human cognitive neuroscience
unit, Northumbria University, Newcastle-upon Tyne.
Several species of ginseng are used medicinally, including Panax
ginseng,
P quinquefolius and P notoginseng. They are used extensively in all Asian
systems of medicine and, in the West, are used in herbal medicine as
a general tonic.
While animal studies have demonstrated effects on behaviour and learning,
such as improved endurance and reactions to experimentally induced stress
and improvements in learning, there is not yet much clinical evidence
of efficacy for ginseng. Many clinical studies have been carried out,
but most have methodological flaws, fail to adequately describe the ginseng
products tested and have used arbitrary doses.
Against this background, Dr Kennedy’s group has undertaken several
preliminary studies exploring the cognitive effects of single doses of
a P ginseng extract G115 (Pharmaton). In a randomised, double-blind,
placebo-controlled, crossover study, 20 healthy volunteers received different
doses of ginseng extract (200, 400 and 600mg) and underwent a battery
of tests designed to assess cognitive effects at 1, 2.5, 4 and 6 hours
post dose. A statistically significant improvement in secondary memory
was observed following administration of the 400mg dose at all time points,
compared with placebo administration. Another study using the same design,
but involving the administration of different doses (320, 640 and 960mg)
of a combination preparation containing ginseng and ginkgo extracts,
produced similar results for the highest dose.
And a further randomised, double-blind, placebo-controlled, crossover
trial involving small numbers of healthy volunteers had suggested that
a single dose of ginseng extract (G115) 200mg could directly modulate
cerebroelectrical activity as recorded on an electroencephalogram to
a greater extent than could ginkgo extract (GK501) 360mg or placebo.
Concluding, Dr Kennedy said he is certain that “ginseng does something,
but we don’t know exactly what”.
Plants in alcohol dependence?
Dr Amir Rezvani, department of psychiatry, Duke University Medical Centre,
North Carolina, discussed whether plant extracts could help treat alcohol
dependence. Medicinal plants have been used for the treatment of alcohol
dependence in Eastern cultures for centuries, but have only recently
attracted interest in the West.
Since alcoholism has neurochemical similarities with depression, such
as low brain serotonin concentrations, extracts of the herbal antidepressant
St John’s wort have been investigated in various animal models
of alcohol dependence. These models include selectively bred alcohol-preferring
rats and high-alcohol-drinking rats, as well as other models which are
not selectively bred, such as the African green monkey, which
drinks alcohol if given a free choice of ethanol and water. Dr Rezvani
described a series of experiments which showed that oral or intraperitoneal
administration of St John’s wort extract reduced alcohol intake
in these models and prevented the alcohol deprivation effect (excessive
alcohol drinking following a period of forced abstinence).
Other studies have demonstrated that puerarin, an isoflavone C-glycoside,
found in the kudzu plant (Pueraria lobata), and ibogaine, an indole alkaloid
found in the root bark of the African shrub iboga (Tabernanthe iboga),
and an ibogaine analogue, 18-methoxycoronaridine, also reduce alcohol
intake in alcohol-preferring rats.
The precise mechanisms of action for the effects of these substances
on alcohol intake are not fully understood, although modulation of serotonergic
or dopaminergic systems, or both, may be involved, said Dr Rezvani. Summing
up, he said that well-designed clinical trials are required to determine
whether any of these substances have a role in the treatment of alcoholism
in humans.
Testing plants for cognitive effects
Continuing one of the session’s themes of cognitive effects of
medicinal plants in humans, Professor Keith Wesnes, chief executive of
Cognitive Drug Research Ltd, described some of his work using a computerised
automated system his group has developed to assess the cognitive effects
of various plants.
The system comprises a battery of tasks and functions designed to assess
attention, concentration and vigilance, working memory and episodic secondary
memory, and has been used in trials for almost 20 years.
Some of Professor Wesnes’ early work had demonstrated that nicotine
improves cognitive function, and more recent studies have described cognitive
effects for sage oil, lemon balm, and rosemary and lavender essential
oils. One particular study reported cognitive effects of a combination
preparation (Pharmaton) of the ginseng extract G115, other herbs and
minerals, administered to nurses working night shifts. Participants received
the combination preparation, or placebo, and underwent computerised cognitive
assessment before and after each of three night shifts.
Concluding, he said that certain plant substances can enhance various
aspects of cognitive function, and that the optimal tests to measure
these effects are properly automated procedures.
— Contributed. |
