The dose‐dependent analgesic effects, abuse liability, safety and tolerability of oral cannabidiol in healthy humans

Author(s):  
Caroline A. Arout ◽  
Margaret Haney ◽  
Evan S. Herrmann ◽  
Gillinder Bedi ◽  
Ziva D. Cooper
1997 ◽  
Vol 24 (1-2) ◽  
pp. 215-216
Author(s):  
John W. Newcomer ◽  
Joy Coleman ◽  
Neil Bhargava ◽  
Gregg Selke ◽  
Angela Kelly ◽  
...  

1999 ◽  
Vol 57 (3B) ◽  
pp. 753-760 ◽  
Author(s):  
TEREZINHA DE JESUS T. SANTOS ◽  
CARLOS M. DE CASTRO-COSTA ◽  
SÍLVIO D. A. GIFFONI ◽  
FRANKLIN J. C. SANTOS ◽  
RODRIGO S. N. RAMOS ◽  
...  

Baclofen (beta-p-chlorophenyl-GABA) has been used in humans to treat spasticity, as well as trigeminal neuralgia. Since GABA (gamma-aminobutyric acid) has been implicated in inhibitory and analgesic effects in the nervous system, it was of interest to study the effect of baclofen in experimental neuropathic pain. With this purpose, experiments were carried out in 17 neuropathic rats with constrictive sciatic injury, as described by Bennet and Xie (1988), taking as pain parameters scratching behaviour and the latency to the thermal nociceptive stimulus. The results showed that baclofen induces, in a dose-dependent manner, significant decrease (p < 0.05) of scratching behaviour and significant increase (p < 0.05) of the latency to the nociceptive thermal stimulus. The absence of antagonism of naloxone suggested a non-participation of an opioid-mediated mechanism in this analgesic effect of baclofen on experimental neuropathic pain.


2010 ◽  
Vol 9 (3) ◽  
pp. 28
Author(s):  
Sh. M. Al-khazrji , and I. K. Khalil

The present study was aimed to investigate the analgesic effects of the aqueous extract of Artemisia herba alba Arial part in rats and mice ( AEAHA ). The AEAHA (400- 700 mg/kg; p.o.) was evaluated for its analgesic activity by employing acetic acid-induced writhing test, hot plate test and tail immersion tests i.e. in hot and cold water. AEAHA (400- 700 mg/kg; p.o.) showed significant (P<0.01) reduction in the number of writhing induced by acetic acid,increased reaction time in hot plate test and elevated pain threshold in hot and cold water tests. AEAHA exhibited the dose-dependent analgesic effects


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A254-A254
Author(s):  
Soraya Allas ◽  
Michel Ovize ◽  
Michael D Culler ◽  
Clarisse Geraul ◽  
Jeroen van de Wetering ◽  
...  

Abstract Hypoparathyroidism is a rare disease characterized by a deficiency in parathyroid hormone (PTH) that results in hypocalcemia and hyperphosphatemia. Current treatment approaches, including high dose oral calcium and active vitamin D, as well as recombinant human PTH (1–84), do not provide adequate or consistent control of either serum calcium or clinical symptoms over a full 24-hour period. AZP-3601 is a novel 36 amino-acid PTH analog that has been designed to potently bind to the R0 conformation of the PTH1 receptor, which results in prolonged signaling responses in vitro and prolonged calcemic responses in animals despite having a short circulating half-life. A Phase 1 double-blind, placebo-controlled, single and multiple ascending dose study is being conducted to evaluate the safety, tolerability and pharmacodynamics of AZP-3601 in healthy adults. Here we report data from the first cohorts of the single ascending dose portion of the study. Sequential cohorts of 4 (cohort 1) to 8 (cohort 2 to 4) healthy male subjects aged 18–60 years, with a body mass index of 19–28 kg/m2, were assigned to receive 5, 10, 20 or 40μg of AZP-3601 or placebo at a ratio of 3:1. The study drug was administered in the morning by subcutaneous injection in the abdominal wall and was well tolerated with no remarkable adverse events. As compared with placebo controls, AZP-3601 treatment produced a clear, dose-dependent increase in mean albumin-adjusted serum calcium values from baseline. The normal physiological diurnal variation of albumin-adjusted serum calcium was gradually attenuated with 5 and 10μg AZP-3601, and was completely eliminated with 20μg. With the dose of 40μg AZP-3601, mean albumin-adjusted serum calcium values were significantly increased but stayed within normal laboratory range and remained elevated through at least 24 hours post-administration. We observed a dose-dependent decrease in mean endogenous serum PTH that was significantly correlated with the concomitant increase in mean serum calcium. These data provide initial evidence of the pharmacodynamic effect of AZP-3601 in healthy humans characterized by a sustained calcemic response for at least 24 hours following a single administration.


2013 ◽  
Vol 6 (1) ◽  
pp. 21-26 ◽  
Author(s):  
Most. Chand Sultana Khatun ◽  
M Ripon Mia ◽  
M Ashraf Ali ◽  
M Moshiur Rahman ◽  
Khadiza Begum ◽  
...  

Background and purposes: Glycosmis pentaphylla (Retz.) Correa, a medicinal plant is popularly used as herbal remedy for various ailments in Bangladesh. It was also reported that GP has both anti-hyperglycemic and analgesic effects and being widely used to reduce blood glucose and to alleviate pain for many years in this region though published literatures are scarce. The present study was designed to evaluate whether ethanolic extract of Glycosmis pentaphylla (GP) have antihyperglycemic and analgesic effects. A total of 60 Swiss Albino male mice of nine weeks (weight, 20-25g) were used for investigation. Of them, 40 were made diabetic by alloxan. They were investigated in two groups – a) 20 mice by oral glucose tolerance test (4 samples OGTT) – at 0, 30, 90 and 120 min; and b) 20 mice for a week-long antihyperglycemic activity on day 0, 1, 3 & 7. Both the groups were subdivided into four, each having 5 mice – i) the ‘control’ received only 0.5% methyl cellulose as vehicle; ii) ‘Standard’ received vehicle plus metformin; iii & iv) test ‘DGP250’ & ‘DGP500’ received vehicle plus GP extract with 250 & 500 mg /kg, respectively. For the analgesic activity, 20 mice were investigated in four subgroups, each having 5 mice and similar steps were adopted. Here, vehicle was used 1% Tween 80 and intra-peritoneal injection of Acetic acid for eliciting pain in all four subgroups. The ‘standard’ group got diclofenac sodium for comparison with the test groups ‘GP250’ and ‘GP500’. In OGTT, Ethanolic extract of GP250 and GP500 reduced blood glucose at 90 min. But the levels of reduction were more significant at 120 min, 50.7% by GP250 and 66% by GP500 (p<0.001). The reduction is almost comparable with that induced by metformin. Likewise, for a weeklong anti-hyperglycemic activity, the GP extracts were found as equally effective as metfomin, which was also dose dependent. In addition to antihyperglycemic effect, the ethanolic extract of GP showed significant analgesic effect that was also dose dependent. Our results indicate that GP extract has antihyperglycemic effect in both short and in weeklong duration, which is almost comparable to Metformin HCL, a known and widely used antihyperglycemic agent. The GP extract was also found to have an analgesic effect almost comparable to diclofenac sodium, a known analgesic drug. Further study is needed to confirm the anti-hyperglycemic and analgesic effect of GP including its side effects in long term use. DOI: http://dx.doi.org/10.3329/imcj.v6i1.14721 Ibrahim Med. Coll. J. 2012; 6(1): 21-26


2005 ◽  
Vol 103 (4) ◽  
pp. 845-854 ◽  
Author(s):  
Philippe Richebé ◽  
Cyril Rivat ◽  
Cyril Creton ◽  
Jean-Paul Laulin ◽  
Pierre Maurette ◽  
...  

Background Although opioids are unsurpassed analgesics for surgery, they also induce an N-methyl-D-aspartate-dependent enhancement of postoperative hyperalgesia. Because nitrous oxide (N2O) has anti-N-methyl-D-aspartate properties, the purpose of this study was to evaluate nitrous oxide ability to prevent such an opioid-induced hyperalgesia in rats. Methods First, preventive effects of 50/50% N2O-O2 on the development of delayed hyperalgesia observed after inflammatory pain (hind paw carrageenan injection on D0) were examined for several days. Second, the ability of nitrous oxide (10-40%) to limit opioid-induced hyperalgesia induced by fentanyl was evaluated in nonsuffering rats. Third, antihyperalgesic effects of various nitrous oxide concentrations (20-50%) were assessed in both inflammatory and incisional pain models in fentanyl-treated rats (4 x 100 microg/kg subcutaneously). Finally, the analgesic effect of a single dose of morphine was evaluated 24 h after fentanyl administration and nitrous oxide (D0) to assess its preventive effect on acute morphine tolerance in both nonsuffering and hind paw-incised rats. Results When applied on D0, nitrous oxide reduced delayed hyperalgesia induced by inflammation. Exposure to nitrous oxide on D0 also reduced opioid-induced hyperalgesia in nonsuffering rats in a dose-dependent manner. In fentanyl-treated rats with inflammatory or incisional pain, nitrous oxide strongly limited both magnitude and duration of hyperalgesia. Moreover, nitrous oxide exposure on D0 opposed development of acute tolerance to analgesic effects of morphine administered on D1 in both nonsuffering and incised fentanyl-treated rats. Conclusions Nitrous oxide, an N-methyl-D-aspartate receptor antagonist, prevented the enhancement of pain sensitivity induced by both nociceptive inputs and fentanyl and opposed acute morphine tolerance. Results suggest that perioperative nitrous oxide use reduces exaggerated postoperative pain and morphine consumption.


Scientifica ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
A. Y. Kabiru ◽  
G. F. Ibikunle ◽  
D. A. Innalegwu ◽  
B. M. Bola ◽  
F. M. Madaki

Antiplasmodial and analgesic effects of crude ethanol extract ofPiper guineensewas investigated in mice. The antiplasmodial and analgesic efficacy of the extract was judged on its ability to reduce parasitemia and writhing, respectively, in mice. The antiplasmodial screening involved treating infected mice with 200, 400, and 600 mg/kg body weight of extract while the positive control group was given standard artesunate drug. The analgesic test was carried out by administering 1000, 1500, and 2000 mg/kg body weight of extract to three groups of healthy mice, respectively, after induction of pain with 0.75% acetic acid. The positive control group was given aspirin drug. Parasitemia was reduced by 28.36%, 43.28%, and 62.69% in a dose-dependent pattern in the curative test which was significantly different (P<0.05) from 96.03% of the standard drug. The reduction of writhing by mice given the extract was also dose-dependent (36.29, 45.43, and 59.07%). Aspirin drug was however more effective (86.36%). The extract was safe at 2000 mg/kg body weight. Phytochemical screening revealed the presence of flavonoids, tannins, phlobatannins, terpenoids, and coumarins. Result obtained in this study demonstrated the efficacy of ethanol extract ofPiper guineenseas an antiplasmodial and analgesic agent.


2019 ◽  
Vol 203 ◽  
pp. 60-69 ◽  
Author(s):  
Kristin J. Schoepfer ◽  
Caroline E. Strong ◽  
Samantha K. Saland ◽  
Katherine N. Wright ◽  
Mohamed Kabbaj

2019 ◽  
Author(s):  
Andrew Kruegel ◽  
Rajendra Uprety ◽  
Steve Grinnell ◽  
Cory Langreck ◽  
Elizabeth Pekarskaya ◽  
...  

<p><i>Mitragynina speciosa</i>, more commonly known as kratom, is a plant native to Southeast Asia, the leaves of which have been used traditionally as a stimulant, analgesic, and treatment for opioid addiction. Recently, growing use of the plant in the United States and concerns that kratom represents an uncontrolled drug with potential abuse liability, have highlighted the need for more careful study of its pharmacological activity. The major active alkaloid found in kratom, mitragynine, has been reported to have opioid agonist and analgesic activity <i>in vitro</i> and in animal models, consistent with the purported effects of kratom leaf in humans. However, preliminary research has provided some evidence that mitragynine and related compounds may act as atypical opioid agonists, inducing therapeutic effects such as analgesia, while limiting the negative side effects typical of classical opioids. Here we report evidence that an active metabolite plays an important role in mediating the analgesic effects of mitragynine. We find that mitragynine is converted <i>in vitro </i>in both mouse and human liver preparations to the much more potent mu-opioid receptor agonist 7-hydroxymitragynine, and that this conversion is mediated by cytochrome P450 3A isoforms. Further, we show that 7-hydroxymitragynine is formed from mitragynine in mice and that brain concentrations of this metabolite are sufficient to explain most or all of the opioid-receptor-mediated analgesic activity of mitragynine. At the same time, mitragynine is found in the brains of mice at very high concentrations relative to its opioid receptor binding affinity, suggesting that it does not directly activate opioid receptors. The results presented here provide a metabolism-dependent mechanism for the analgesic effects of mitragynine and clarify the importance of route of administration for determining the activity of this compound. Further, they raise important questions about the interpretation of existing data on mitragynine and highlight critical areas for further research in animals and humans.</p>


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