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Recent literature regarding drug-drug, herb-drug, and food-drug interactions must not be ignored; nor can they always be taken at face value. Studies have shown that St. John's wort (SJW)(Hypericum perforatum) can reduce plasma levels of indinavir, cyclosporin, digoxin, and possibly other drugs as well. Current knowledge regarding the metabolism of these medications suggests that the cytochrome P450 (CYP) drug metabolizing enzyme systems cannot account for all these effects. It has been reported that the P-glycoprotein (Pgp) transmembrane pump is also induced by SJW. Medications that are substrates of both CYP 3A4 a Pgp are of particular concern and may pose special interaction risks when combined with certain foods or botanical products such as SJW.

Valerian is a botanical used for its sedative effects whose central nervous system activity is ascribed to multiple constituents. Twenty-three established outpatient symptomatic Hispanic volunteers receiving mental health services at a large urban hospital participated in this case study. All complained of insufficient sleep. They were asked to try a popular national brand of valerian ("Nature's Way", 470 mg valerian root) and completed sleep questionnaires at baseline and at the end of Weeks 1 and 2. They were instructed to take 1 capsule each night before retiring and were allowed to increase their dose to a maximum of 3 capsules after Week 1. Twenty patients completed the trial. On an ordinal scale of 1 (no effect), 3 (moderately helpful), and 5 (extremely helpful), 16 patients rated their insomnia as at least "moderately improved" at the end of Week 1. By Week 2, 16 still rated themselves at least "moderately improved," but 15 of them now described their response as either a 4 or a 5. Global improvement at Week 2 was significantly better than at Week 1 (Wilcoxon ranks test p = .005), perhaps reflecting a time-dependent or dose-response relationship. This case study suggests that valerian can be a supplement for improving insomnia in a symptomatic population.

Alternative therapies are widely used by consumers. A number of herbs and dietary supplements have demonstrable effects on mood, memory, and insomnia. There is a significant amount of evidence supporting the use of Hypericum perforatum (St. John's wort) for depression and Ginkgo biloba for dementia. Results of randomized, controlled trials also support the use of kava for anxiety and valerian for insomnia. Although evidence for the use of vitamins and amino acids as sole agents for psychiatric symptoms is not strong, there is intriguing preliminary evidence for the use of folate, tryptophan, and phenylalanine as adjuncts to enhance the effectiveness of conventional antidepressants. S-adenosylmethionine seems to have antidepressant effects, and omega-3 polyunsaturated fatty acids, particularly docosahexaenoic acid, may have mood-stabilizing effects. More research should be conducted on these and other natural products for the prevention and treatment of various psychiatric disorders.

SJW is a remarkably safe antidepressant with an apparently unique mode of action. Although it has demonstrated efficacy in mild and moderate depression when compared with placebo or tricyclic antidepressants, several research areas beg to be explored. Its effects should be compared with serotonin reuptake inhibitors. Studies in severely depressed patients are lacking, as are studies on its utility as a therapeutic adjunct to standard antidepressants.

Thyrotropin releasing hormone (TRH) antagonizes the behavioral and temperature reducing effects of pentobarbital in rodents. The hormone is effective whether given before or after the barbiturate. This antagonism by TRH of the effects of pentobarbital probably does not depend upon thyroid hormone release as L-triiodothyronine administration is ineffective.

Both thyrotropin-releasing hormone (TRH) and amphetamine antagonize pentobarbital. They are more effective in the day than at night. This is true for TRH even when the dose of pentobarbital is increased at night to prolong sedation. Under this condition the day-night difference is lost for amphetamine. Both substances are more effective in cold ambient temperatures (18 degrees C) and less effective in warm temperatures, but their activity at warmer temperatures (37 degrees C) is still substantial. In contrast, somatotropin release-inhibiting factor (SRIF) augments the effects of pentobarbital at room temperature. This action is unaffected by time of day. However, the increase in sleeping time is lost in both a warm environment and in a cold environment.

Thyrotropin releasing hormone (TRH) antagonizes pentobarbital sedation and hypothermia; somatotropin release inhibiting factor amplifies them. Other hypothalamic polypeptide releasing factors, Substance P and a variety of amino acids are ineffective. Three congeners of TRH antagonize pentobarbital; one amplifies it. The potencies of congeners as pentobarbital antagonists are unrelated to their potencies as pituitary thyrotropin releasers.

Changes in electrical self-stimulation responding were examined in rats with electrodes implanted in the lateral hypothalamus following 6-hydroxydopamine treatments which depleted brain dopamine, norepinephrine or both of these catecholamines. Acute depression of self-stimulation occurred after treatments which reduced brain dopamine, but did not occur in rats treated to deplete just brain norepinephrine. A chronic deficit in self-stimulation responding occurred in rats treated with 6-hydroxydopamine in combination with pargyline to reduce both brain amines, while responding of animals in which brain dopamine was reduced returned to levels observed prior to 6-hydroxydopamine treatment. A dose of α-methyl-tyrosine (25 mg/kg), which did not affect responding of control rats, caused a significant reduction in responding of rats depleted of brain dopamine. This treatment did not affect responding of rats depleted of brain norepinephrine. Administration of the dopamine-Β-hydroxylase inhibitor, U-14624, failed to affect self-stimulation in spite of an additional 70% reduction of brain norepinephrine content. The response to a dose of d-amphetamine (0.25 mg/kg), that increased self-stimulation of control rats, was significantly reduced in rats with brain dopamine selectively depleted. Rats in which norepinephrine was depleted responded to d-amphetamine like the control group. α-Methyltyrosine antagonized the increased self-stimulation responding following administration of d-amphetamine (1 mg/kg) to reserpinized rats, while U-14624 did not. Results support the hypothesis that central dopaminergic fibers have an important involvement in the maintenance of self-stimulation of brain.

Thyrotropin releasing hormone (TRH) reduced the narcosis and hypothermia produced by ethanol in mice. This action of TRH does not appear related to release of thyroid hormone or to the effects of a metabolite of TRH. The ability of TRH to reduce the actions of ethanol after intracisternal injection suggests that the mechanism of the ethanol antagonism is central in origin. The antagonism of ethanol by TRH does not appear to be related to an amphetamine-like stimulant action.

Administration of 10 mg/kg TRH to mice was found to reduce the sleep and hypothermia induced by 4.7 g/kg ethanol. However, TRH did not reduce the sleep of mice that were given gamma-hydroxybutyric acid (GHBA), baclophen, or aminooxyacetic acid (AOAA) in combination with 3 g/kg/ ethanol. TRH also failed to reverse the hypothermia induced by the combination of ethanol and baclophen or GHBA, and the characteristic neurological effects of TRH e.g. tremor, increased muscle tone, and increased respiratory rate were reduced. In addition, TRH-induced locomotor stimulation was prevented by pretreatment with small doses of the GABA-ergic agents, and while 30 mg/kg TRH reduced the hypothermia produced by large doses of the GABA-ergic drugs, it did not antagonize the locomotor retardation produced by baclophen or GHBA. A hypothesis that the analeptic effects of TRH may be medicated via an inhibition of GABA systems is discussed.