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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The synthesis of a variety of novel 10-substituted cannabidiol (CBD) and 11- or 12-substituted delta 8-tetrahydrocannabinol (delta 8-THC) analogues containing amino, alkylamino, azido, or a N,N-bis(2-chloroethyl)amino functional group is described, as well as their pharmacological evaluation in mice. These analogues, which possess only a portion of the full pharmacological spectrum of activity of delta 9-THC, indicate that cannabinoid-mediated reduction of spontaneous locomotor activity, hypothermia, antinociception, and/or catalepsy need not be produced simultaneously, possibly suggesting the existence of more than one mechanism of action. The 10-substituted CBD analogues 3, 4, and 5 with an ethylamino, propylamino, or azido functional group, respectively, proved to be largely inactive, except for the production of central nervous system (CNS) depression concomitant with toxicity. Toxicity and CNS depression may be related phenomena in these nitrogenous compounds since 12-amino and 12-ethylamino analogues (8 and 11) of delta 8-THC also proved to be very toxic. Antinociceptive and hypothermic responses (without reduction of motor activity) were observed at a dose of 10 mg/kg of the 11-ethylamino analogue (9) of delta 8-THC, while a dose of 50 mg/kg of the nitrogen mustard 11-[N,N-bis(2-chloroethyl)amino]-delta 8-THC (12) was necessary to produce any observable pharmacological effect. When selected analogues were evaluated for antagonistic properties, they failed to attenuate the effects of delta 9-THC. Some nitrogen mustard analogues were capable of producing minimal pharmacological effects after either peripheral or direct CNS administration; however, these analogues also failed to attenuate the effects of delta 9-THC either immediately after administration or 24-48 h later.
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PMID:Synthesis and pharmacological evaluation of amino, azido, and nitrogen mustard analogues of 10-substituted cannabidiol and 11- or 12-substituted delta 8-tetrahydrocannabinol. 215 63

Administration of delta 9-tetrahydrocannabinol (THC; 0.75-4.0 mg/kg IP) to rhesus monkeys produced a biphasic pattern of high-voltage slow waves (HVSW) and fast waves (HVFW) EEG, along with behavioral depression and alertness, respectively. The HVSW phase appeared 20 to 30 min after drug injection and was uniquely characterized by spike-bursts in frontal and temporal lobes and hypothalamus, theta-waves in parietal and occipital lobes, and generalized HVSW in subcortical regions. During the HVSW phase, bradycardia and hypothermia occurred, and animals exhibited depression or sedation. After the HVSW phase lasting for 3-4 hr, HVFW predominated in overall EEGs with marked decrease in neocortical spike-bursts. Bradycardia and hypothermia occurred simultaneously 20 to 30 min after drug injection and reached maximal levels (30-40 percent decrease in heart rate, 1.5-2.0 degrees C decrease in body temperature) 2 to 3 hr after injection. The dose- and time-response relationships for bradycardia and hypothermia paralleled the HVSW phase with behavioral depression. Animals were alert and calm during recovery from bradycardia and hypothermia. THC levels and disposition in blood correlated with bradycardia, hypothermia and EEGs and behavioral changes following THC administration.
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PMID:delta 9-Tetrahydrocannabinol: EEG changes, bradycardia and hypothermia in the rhesus monkey. 282 7

The present studies examine some of the pharmacological effects of delta-9 (11)-tetrahydrocannabinol (delta 9-11-THC), an analog of delta-9-tetrahydrocannabinol (delta 9-THC). In tests with mice, delta 9-11-THC was similar to but less potent than delta 9-THC in producing hypothermia, analgesia, lethality and in reducing spontaneous activity. In dogs delta 9-THC but not delta 9-11-THC produced classical cannabimimetic signs including static ataxia, hyperreflexia, prancing and tail-tuck. delta 9-11-THC did produce central nervous system depression in 9 of the 15 dogs tested but the effects were not dose-related and appeared earlier and dissipated faster than the depressive effects induced by delta 9-THC. delta 9-THC but not delta 9-11-THC produced signs of ptosis, sedation and ataxia in rhesus monkeys. delta 9-THC also suppressed operant responding completely in four of four monkeys tested whereas in one monkey delta 9-11-THC did not do so up to doses as high as 5.0 mg/kg and was 8 to 100 times less potent in doing so in the other monkeys. When monkeys were pretreated with delta 9-11-THC the doses of delta 9-THC required to produce ptosis, sedation, ataxia and operant suppression were increased. However, when mice and dogs were pretreated with delta 9-11-THC the effects of delta 9-THC were not attenuated and usually were enhanced. The pharmacological profile of delta 9-11-THC is unusual in that it seems to have cannabimimetic activity in mice, noncannabimimetic-like effects in dogs and is perhaps devoid of cannabimimetic effects in rhesus monkeys. In addition, pretreatment with delta 9-11-THC attenuates the cannabimimetic effects of delta 9-THC in rhesus monkeys but not in mice or dogs.
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PMID:Studies on the agonistic activity of delta 9-11-tetrahydrocannabinol in mice, dogs and rhesus monkeys and its interactions with delta 9-tetrahydrocannabinol. 303 18

In rhesus monkeys, acute administration of levonantradol and nantradol produced signs of CNS depression, including ataxia with body sag, pupil dilation, ptosis, dozing, and reduced responsivity to external stimuli. Neither compound suppressed the morphine withdrawal syndrome; however, both alleviated the chronic abdominal contraction associated with withdrawal. The directly observable effects of these compounds were not antagonized by naloxone. When levonantradol was administered every 6 hours, marked tolerance developed to both the effects of levonantradol and nabilone and THC. No signs of withdrawal were observed when levonantradol injections were abruptly discontinued. When substituted in lieu of codeine under an intravenous drug self-administration procedure, neither levonantradol nor nantradol maintained responding at rates higher than those maintained by their vehicle. Finally, the discriminative effects of levonantradol were not equivalent to those of the narcotics ethylketazocine or etorphine.
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PMID:Behavioral effects of levonantradol and nantradol in the rhesus monkey. 627 36

Recent breakthroughs in cannabinoid research, including the identification of two cannabinoid receptors (CB receptors) and a family of endogenous ligands, the anandamides, may shed new light on the sequelae of pre- and perinatal exposure to cannabinoid receptor ligands and enable the experimental manipulation of the endogenous ligand in the developing organism. In the present study we examined the behavioural response to anandamide (ANA) in developing mice from day 13 into adulthood. We observed that depression of ambulation in an open field and the analgetic response to ANA are not fully developed until adulthood. In a separate set of experiments, we administered five daily injections of ANA (SC, 20 mg/kg) during the last trimester of pregnancy. No effects on birth weight, litter size, sex ratio and eye opening were detected after maternal ANA treatment. Further, no effects on open field performance of the offspring were observed until 4 weeks of age. However, from 40 days of age, a number of differences between the prenatal ANA and control offspring were detected. Thus, the offspring from ANA-treated dams showed impaired responsiveness to a challenge with ANA or delta 0-THC expressed as a lack of immobility in the ring test for catalepsy, hypothermia and analgesia. On the other hand, without challenge, they exhibited a spontaneous decrease in open field activity, catalepsy, hypothermia and a hypoalgetic tendency. These data suggest that exposure to excessive amounts of ANA during gestation alters the functioning of the ANA-CB receptor system. Further experiments investigating responsivity of the immune system suggest an increased inflammatory response to arachidonic acid, and enhanced hypothermic response to lipopolysaccharide in prenatally treated offspring. The results are discussed in relation to other manipulations of the maternal milieu, especially prenatal stress. It is concluded that alterations induced by prenatal exposure to ANA, cannabinoids and other psychotropic drugs or prenatal stress, share common features, but the data also suggest specific effects on the ANA-CB receptor system.
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PMID:Developmental aspects of anandamide: ontogeny of response and prenatal exposure. 877 60

Cannabis has a potential for clinical use often obscured by unreliable and purely anecdotal reports. The most important natural cannabinoid is the psychoactive tetrahydrocannabinol (delta9-THC); others include cannabidiol (CBD) and cannabigerol (CBG). Not all the observed effects can be ascribed to THC, and the other constituents may also modulate its action; for example CBD reduces anxiety induced by THC. A standardised extract of the herb may be therefore be more beneficial in practice and clinical trial protocols have been drawn up to assess this. The mechanism of action is still not fully understood, although cannabinoid receptors have been cloned and natural ligands identified. Cannabis is frequently used by patients with multiple sclerosis (MS) for muscle spasm and pain, and in an experimental model of MS low doses of cannabinoids alleviated tremor. Most of the controlled studies have been carried out with THC rather than cannabis herb and so do not mimic the usual clincal situation. Small clinical studies have confirmed the usefulness of THC as an analgesic; CBD and CBG also have analgesic and antiinflammatory effects, indicating that there is scope for developing drugs which do not have the psychoactive properties of THC. Patients taking the synthetic derivative nabilone for neurogenic pain actually preferred cannabis herb and reported that it relieved not only pain but the associated depression and anxiety. Cannabinoids are effective in chemotherapy-induced emesis and nabilone has been licensed for this use for several years. Currently, the synthetic cannabinoid HU211 is undergoing trials as a protective agent after brain trauma. Anecdotal reports of cannabis use include case studies in migraine and Tourette's syndrome, and as a treatment for asthma and glaucoma. Apart from the smoking aspect, the safety profile of cannabis is fairly good. However, adverse reactions include panic or anxiety attacks, which are worse in the elderly and in women, and less likely in children. Although psychosis has been cited as a consequence of cannabis use, an examination of psychiatric hospital admissions found no evidence of this, however, it may exacerbate existing symptoms. The relatively slow elimination from the body of the cannabinoids has safety implications for cognitive tasks, especially driving and operating machinery; although driving impairment with cannabis is only moderate, there is a significant interaction with alcohol. Natural materials are highly variable and multiple components need to be standardised to ensure reproducible effects. Pure natural and synthetic compounds do not have these disadvantages but may not have the overall therapeutic effect of the herb.
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PMID:Cannabinoids in clinical practice. 1115 13

Many people living with HIV use marijuana to manage agitation, spasms, chronic pain, depression, nausea arising from chemotherapy, and loss of appetite. Concerns over the use of marijuana or dronabinol (a pharmaceutical version of tetrahydrocannabinol or THC) include potential contamination from pesticides or other chemicals used in the growing process, and the potential of increasing the likelihood of lung infections. Use of THC is associated with reduced levels of testosterone and may have similar effects on other hormones in women. THC can also interact with other mood-altering medications such as Valium, librium, Xanax, seconal, Nembutal, or phenobarbital, by exaggerating their effect.
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PMID:Medical marijuana and dronabinol. 1136 69

Although the majority of cannabinoid users smoke marijuana, the preponderance of laboratory animal research is based on administration of Delta9-tetrahydrocannabinol (Delta9-THC) or other cannabinoid agents via injection. The aim of the present study was to evaluate the impact of inhaling marijuana, or ethanol-extracted placebo smoke in the mouse model of cannabinoid activity by assessing inhibition of spontaneous activity, antinociception, catalepsy, and body temperature. In order to determine dosimetry, blood levels of Delta9-THC were obtained following either marijuana exposure or intravenous injection of Delta(9)-THC. Inhalation exposure to marijuana produced dose-related increases in antinociception and catalepsy, with estimated ED50 doses of Delta9-THC of 2.4 and 3.8 mg/kg, respectively. However, hypothermia and locomotor depression occurred in both the placebo- and marijuana-exposed mice. The CB1 receptor antagonist, SR 141716A antagonized the antinociceptive effects of marijuana (AD50 = 0.6 mg/kg), but only slightly decreased marijuana-induced catalepsy, and failed to alter either the hypothermic or locomotor depressive effects. In contrast, SR 141716A antagonized the antinociceptive, cataleptic, and hypothermic effects of intravenously administered Delta9-THC in mice that were exposed to air alone, though all subjects exhibited locomotor depression, possibly related to the restraint. In accordance with reports of others, these data suggest that exposure to smoke alone has pharmacological consequences. Our findings also indicate that marijuana-induced antinociception is mediated through a CB1-receptor mechanism of action and are consistent with the notion that Delta9-THC is mainly responsible for this effect.
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PMID:The pharmacological activity of inhalation exposure to marijuana smoke in mice. 1137 14

Addition of nitrite-N at 1.5 mg l(-1) in tryptic soy broth (TSB) significantly (p < 0.05) decreased the growth rate of the bacterial pathogen Lactococcus garvieae and significantly (p < 0.05) reduced mortality compared to zero nitrite controls when injected into giant freshwater prawns Macrobrachium rosenbergii at 5 x 10(5) colony-forming units (CFU) per prawn. In other experiments, whereby prawns were injected with TSB-grown L. garvieae (5 x 10(5) CFU prawn(-1)) and then held in water containing nitrite-N, mortality at 72 h post-injection was significantly (p < 0.05) higher for prawns held in water containing 1.68 mg l(-1) nitrite than at lower concentrations. Prawns exposed to different concentrations of nitrite-N were examined for THC (total hemocyte count), phenoloxidase activity, respiratory burst, phagocytic activity and bacterial clearance efficiency. No significant differences in THC and phenoloxidase activity were observed among treatments. With prawns exposed to nitrite-N for 168 h (7 d) at 1.59 mg l(-1), phagocytic activity and clearance efficiency decreased, while at 1.15 mg l(-1) or more, respiratory burst increased, generating the superoxide anion at levels considered cytoxic to the host. We conclude that nitrite-N at 1.68 mg l(-1) causes depression in the immune response and increased mortality in M. rosenbergii infected with L. garvieae.
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PMID:Effect of nitrite on interaction between the giant freshwater prawn Macrobrachium rosenbergii and its pathogen Lactococcus garvieae. 1221 75

Longterm use of marijuana has been found to cause physiological changes that can alter individual reproductive potential. The effects of marijuana depend on the dose and can include death from depression of the respiratory system. Longterm effects are however particularly hard to assess. Marijuana is absorbed rapidly and eliminated very slowly. The active principle, delta-9-tetrahidrocannabinol (delta-9-THC), is highly liposoluble and fixes to the serum proteins, passing to the lungs and liver for metabolization and to the kidneys and liver for excretion. As with estrogens, there is an enterohepatic circuit for reabsorption and elimination. 90% is eliminated in the feces, 65% within 48 hours. Because of the enterohepatic circuit and liposolubility, elimination requires 1 week for completion. The other important biotransformation of the active principle is hydroxilation; the hydroxilated derivatives are responsible for the psychoactivity of cannabis. Cannabis affects both neuroendocrine function and the germ cells. Studies on experimental animals have indicated that THC can cause a decline in the pituitary hormones follicle stimulating hormone, luteinizing hormone, and prolactin, and in the steroids progesterone, estrogen, and androgens. Human studies have shown that chronic users have decreased levels of serum testosterone. Because steroidogenesis can be restimulated with human chorionic gonadotropin, it appears that THC does not directly affect steroid production by the corpus luteum, but that its action is mediated by the hypothalamus. Because of its potent antigonadotropic action, THC is under study as an anovulatory agent. The same animal studies have shown that ovulation returns to normal 6 months after termination of use. High rates of anovulation and luteal insufficiency have been observed in women smoking marijuana at least 3 times weekly. THC accumulates in the milk. Animal studies have shown that THC depresses the enzymes necessary for lactation and causes a diminution in the volume of the mammary glands. In recent studies, significant amounts of the drug have been detected in both mothers' milk and the blood of newborns. Animal studies indicate that THC crosses the placenta, achieving concentrations in the fetus as high as those in the mother. Animal studies also demonstrated increasing frequency of abortions, intrauterine death, and declines in fetal weight. The effects were probably due to an alteration in placental function. A human study likewise showed that marijuana use during pregnancy was significantly related to poor fetal development, low birth weight, diminished size, and decreased cephalic circumference. Congenital malformations have been observed in experimental animals exposed to THC. Declines in sperm volume and count and abnormal sperm motility have been observed in chronic marijuana users. In vitro studies show that THC produces a marked degeneration of human sperm.
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PMID:[Review and update: marijuana and reproduction]. 1228 Dec 77


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