Related case:

TJD-AD 2023-003 Disciplinary Decision - Basketball
August 3, 2023


On 3 August 2023 the Brazilian Sports Justice Anti-Doping Tribunal (TJD-AD) decided to impose a 2 year period of ineligibility on the basketball player after he tested positive for the prohibited substance Cannabis.

Although in first instance the violation was deemed not intentional, the Athlete made no admission and did not accept a provisional suspension. He also failed to demonstrate with evidence that the use of Cannabis occurred out-of-competition.

Hereafter the Athlete appealed the Decision with the TJD-AD Appeal Panel. He requested the Appeal Panel to set aside the Appealed Decision and to impose a reduced sanction, starting on the date of the sample collection.

This time the Athlete admitted the violation and explained that he had used Cannabis for health reasons. With evidence he attempted to demonstrate that he had used the substance out-of-competition in a context unrelated to sport performance.

Considering the evidence in this case the Rapporteur accepts that the violation was not intentional and that the substance was not used in a context to sport performance. However in view of the Athlete's conduct the Rapporteur deems that there are insufficient grounds to reduce the imposed sanction.

Nevertheless the Rapporteur determines that indeed there had been delays in the proceedings not attributed to the Athlete. Consequently this justifies the modification of the starting date of the sanction.

Therefore the TJD-AD Appeal Panel decides on 4 October 2023 to uphold the Appealed Decision and the imposition of a 2 year period of ineligibility. The Appeal Panel decides to modify the starting date of the sanction to be set on the date of the sample collection, i.e. on 17 January 2023.

Related case:

TJD-AD 2023-014 Appeal Decision - Basketball
October, 4, 2023


In January 2023 the Brazilian Doping Control Authority (ABCD) reported an anti-doping rule violation against the basketball player after his sample tested positive for the prohibited substance Cannabis in a concentration above the WADA threshold.

Following notification the Athlete did not accept a provisional suspension. He filed a statement in his defence and the case was referrred to the Brazilian Sports Justice Anti-Doping Tribunal (TJD-AD).

Preliminary the Athlete sought for a sanction under the Substance of Abuse stipulations. However, ABCD proposed a 4 year sanction due to lack of grounds for a reduced sanction.

The Athlete made no admission, nor did he prove that the use of Cannabis occurred out-of-competition. He merely denied the intentional use of Cannabis and argued that the substance does not enhance sport performance.

The Rapporteur finds that the presence of a prohibited substance has been established in the Athlete's sample and accordingly that he committed an anti-doping rule violation.

The Rapporteur deems that there is no evidence that the Athlete acted intentionally. However, he made no admission, neither demonstrated out-of-competion use of Cannabis.

Considering the high concentration found in the Athlete's sample the Rapporteur concludes that violation occurred in-competition. Furthermore the Athlete had not accepted a provisional suspension.

Therefore the TJD-AD Panel decides on 3 August 2023 to impose a 2 year period of ineligibility on the Athlete, starting on the date of the decision.

In June 2023 the Brazilian Doping Control Authority (ABCD) reported an anti-doping rule violation against the weightlifter after he tested positive for the prohibited substances Mestanolone and Stanozolol.

Following notification a provisional suspension was ordered. The Athlete failed to respond and the case was referred to the Brazilian Sports Justice Anti-Doping Tribunal (TJD-AD).

Because the Athlete again failed to respond within the set deadline the Panel finds that the Athlete is deemed to have admitted the asserted violation, waived his right to a hearing and accepted all proposed consequences.

Therefore the TJD-AD Panel decides on 29 September to impose a 4 year period of ineligibility on the Athlete, starting on the date of the provisional suspension, i.e. 27 June 2023.

Related case:

TJD-AD 2023-015 Appeal Decision - Cycling
October 4, 2023

In October 2022 the Brazilian Doping Control Authority (ABCD) reported an anti-doping rule violation against the cyclist after his 2 samples, both collected in September 2022, tested positive for the prohibited substances Prednisolone, Prednisone and Testosterone with its metabolites.

Following notification a provisional suspension was ordered. However ABCD reported that the Athlete had participated in competitions during the imposed provisional suspension.

Thereupon the Athlete did not accept the sanction proposed by ABCD. He filed a statement in his defence and he was heard for the Brazilian Sports Justice Anti-Doping Tribunal (TJD-AD).

The Athlete denied the intentional use of the subsances and requested the Panel to dismiss the charges against him. He stated that he only had used natural products in order to stimulate his endogenous hormone production and libido.

The prosecutor contended that the test results were valid and without departures of the relevant standards. Also the Athlete failed to demonstrate that he acted not intentionally.

The Ahtlete had no TUE and there was evidence that he had breached the imposed provisional suspension. Furthermore the substances found in his sample were exogenous, not endogenous, whereas he had acted negligently with his supplements.

Therefore the TJD-AD Panel decides on 3 August 2023 to impose a 4 year period of ineligibility on the Athlete. Because the Athlete had breached the imposed provisional suspension the Panel by majority decides to impose an additional 2 years on the Athlete. This 6 year period of ineligibility shall start on the of the decision.

Clinical pharmacology of tramadol / Stefan Grond, Armin Sablotzki

• Clinical Pharmacokinetics 43 (2004) 13, p. 879–923
• PMID: 15509185
• DOI: 10.2165/00003088-200443130-00004

Abstract

Tramadol, a centrally acting analgesic structurally related to codeine and morphine, consists of two enantiomers, both of which contribute to analgesic activity via different mechanisms. (+)-Tramadol and the metabolite (+)-O-desmethyl-tramadol (M1) are agonists of the mu opioid receptor. (+)-Tramadol inhibits serotonin reuptake and (-)-tramadol inhibits norepinephrine reuptake, enhancing inhibitory effects on pain transmission in the spinal cord. The complementary and synergistic actions of the two enantiomers improve the analgesic efficacy and tolerability profile of the racemate. Tramadol is available as drops, capsules and sustained-release formulations for oral use, suppositories for rectal use and solution for intramuscular, intravenous and subcutaneous injection. After oral administration, tramadol is rapidly and almost completely absorbed. Sustained-release tablets release the active ingredient over a period of 12 hours, reach peak concentrations after 4.9 hours and have a bioavailability of 87-95% compared with capsules. Tramadol is rapidly distributed in the body; plasma protein binding is about 20%. Tramadol is mainly metabolised by O- and N-demethylation and by conjugation reactions forming glucuronides and sulfates. Tramadol and its metabolites are mainly excreted via the kidneys. The mean elimination half-life is about 6 hours. The O-demethylation of tramadol to M1, the main analgesic effective metabolite, is catalysed by cytochrome P450 (CYP) 2D6, whereas N-demethylation to M2 is catalysed by CYP2B6 and CYP3A4. The wide variability in the pharmacokinetic properties of tramadol can partly be ascribed to CYP polymorphism. O- and N-demethylation of tramadol as well as renal elimination are stereoselective. Pharmacokinetic-pharmacodynamic characterisation of tramadol is difficult because of differences between tramadol concentrations in plasma and at the site of action, and because of pharmacodynamic interactions between the two enantiomers of tramadol and its active metabolites. The analgesic potency of tramadol is about 10% of that of morphine following parenteral administration. Tramadol provides postoperative pain relief comparable with that of pethidine, and the analgesic efficacy of tramadol can further be improved by combination with a non-opioid analgesic. Tramadol may prove particularly useful in patients with a risk of poor cardiopulmonary function, after surgery of the thorax or upper abdomen and when non-opioid analgesics are contraindicated. Tramadol is an effective and well tolerated agent to reduce pain resulting from trauma, renal or biliary colic and labour, and also for the management of chronic pain of malignant or nonmalignant origin, particularly neuropathic pain. Tramadol appears to produce less constipation and dependence than equianalgesic doses of strong opioids.

Simultaneous determination of tramadol, O-desmethyltramadol and N-desmethyltramadol in human urine by gas chromatography-mass spectrometry / Abdel-Aziz Y. El-Sayed, Khaled M. Mohamed, Ahmed Y. Nasser, Jennifer Button, David W. Holt

• Journal of Chromatography B  926 (1 May 2013), p. 9-15
• PMID: 23542669
• DOI: 10.1016/j.jchromb.2013.02.019

Abstract

Analytical procedures for the determination of tramadol (T), O-desmethyltramadol (ODT), and N-desmethyltramadol (NDT) in human urine have been developed and validated using gas chromatography-mass spectrometry (GC/MS). Sample preparation involved liquid-liquid extraction with methyl-tert-butyl ether (MTBE) and followed by back extraction with 0.1 M hydrochloric acid. Proadifen (SKF525A) was selected as internal standard (IS). Extraction efficiencies of T, ODT and NDT were 102.12, 101.30, and 98.21%, respectively. The calibration curves were linear (r(2)>0.99) in the concentration range 10-1000 ng/mL for all compounds. Limits of quantification (LOQ) were 10, 10 and 20 ng/mL for T, ODT and NDT, respectively. Intra-assay precision was within 1.29-6.48% and inter-assay precision was within 1.28-6.84% for T, ODT and NDT. Intra-assay accuracy was within 91.79-106.89% for all analytes. This method detected urine concentrations of T, ODT and NDT in six healthy volunteers for 7 days after administration of 50 mg oral doses of tramadol.

Tramadol hydrochloride : pharmacokinetics, pharmacodynamics, adverse side effects, co-administration of drugs and new drug delivery systems / M. Vazzana, T. Andreani, J. Fangueiro, C. Faggio, C. Silva, A Santini, M.L. Garcia, A.M. Silva, E.B. Souto

• Biomedicine & Pharmacotherapy 70 (March 2015), p. 234-238
• PMID: 25776506
• DOI: 10.1016/j.biopha.2015.01.022

Abstract

Tramadol hydrochloride (TrHC) is a synthetic analgesic drug exhibiting opioid and non-opioid properties, acting mainly on the central nervous system. It has been mostly used to treat pain, although its use to treat anxiety and depression has also been documented. These properties arise from the fact that they inhibit serotonin (5-HT) reuptake augmenting 5-HT concentration on the synaptic cleft. Despite this, TrHC has also been described to have several side effects which are mainly due to its fast metabolization and excretion which in turn requires multiple doses per day. To surpass this limitation, new pharmaceutical formulations are being developed intending the protection, target and sustained delivery as well as a reduction on daily dose aiming a reduction on the side effects. In the present work we have revised the efficacy, safety, biological and adverse effects of TrHC, and the added value of developing a novel drug delivery system for topical administration.

Concentrations of THC, CBD, and CBN in commercial hemp seeds and hempseed oil sold in Korea / Eunyoung Jang, Hyojeong Kim, Seojeong Jang, Jaesin Lee, Seungkyung Baeck, Sanghwan In, Eunmi Kim, Yong-Ung Kim, Eunyoung Han

• Forensic Science International 306 (January 2020), 110064
• PMID: 31786513
• DOI: 10.1016/j.forsciint.2019.110064

Abstract

Hemp seeds and hempseed oil are marketed on- and off-line as health foods and cosmetics and have been reported to have high nutrient contents. However, because of the various side effects of cannabinoids, especially △9-tetrahydrocannabinol (THC), many countries regulate upper limits for THC in products, which creates the need for analytical techniques capable of measuring THC, cannabidiol (CBD), and cannabinol (CBN) levels in commercial hemp seeds and hempseed oil. In the present study, hemp seed and hempseed oil extracts obtained by methanol extraction, were analyzed by gas chromatography-mass spectrometry (GC/MS). Validation of the technique used was performed using calibration curves and by determining LODs, LOQs, specificities, selectivities, and intra- and inter-day precision and accuracies. In addition, matrix effects, process efficiencies, recoveries, and sample stabilities were investigated. In hemp seeds, as determined using the fully optimized method THC concentrations ranged from 0.06 to 5.91 μg/g, CBD concentrations from 0.32 to 25.55 μg/g, and CBN concentrations from 0.01 to 1.50 μg/g; CBN/THC ratios ranged from 0.1 to 1.60, and CBD/THC ratios from 0.11 to 62.56. Furthermore, the (THC + CBN)/CBD ratio of most hemp seed samples was less than one. In hempseed oil, THC concentrations ranged from 0.3 to 19.73 μg/mL, CBD concentrations from 6.66 to 63.40 μg/mL, CBN concentrations from 0.11 to 2.31 μg/mL, CBN/THC ratios from 0.12 to 0.42, and CBD/THC ratios from 3.21 to 22.50. Furthermore, (THC + CBN)/CBD ratios in all hempseed oil samples were less than one. The optimized methanol extraction-GC/MS technique was found to be satisfactory for determining THC, CBD, and CBN concentrations in hemp seeds and hempseed oil.

Cannabis sativa (Hemp) Seeds, Δ9-Tetrahydrocannabinol, and Potential Overdose / Yi Yang, Melissa M. Lewis, Angelica M. Bello, Ewa Wasilewski, Hance A. Clark, Lakshmi P. Kotra

• Cannabis and Cannabinoid Research 2 (2017) 1 (1 October), p. 274-281
• PMID: 29098190
• PMCID: PMC5665515
• DOI: 10.1089/can.2017.0040

Abstract

Introduction:Cannabis sativa (hemp) seeds are popular for their high nutrient content, and strict regulations are in place to limit the amount of potentially harmful phytocannabinoids, especially Δ9-tetrahydrocannabinol (Δ9-THC). In Canada, this limit is 10 μg of Δ9-THC per gram of hemp seeds (10 ppm), and other jurisdictions in the world follow similar guidelines. Materials and Methods: We investigated three different brands of consumer-grade hemp seeds using four different procedures to extract phytocannabinoids, and quantified total Δ9-THC and cannabidiol (CBD). Discussion: We discovered that Δ9-THC concentrations in these hemp seeds could be as high as 1250% of the legal limit, and the amount of phytocannabinoids depended on the extraction procedure employed, Soxhlet extraction being the most efficient across all three brands of seeds. Δ9-THC and CBD exhibited significant variations in their estimated concentrations even from the same brand, reflecting the inhomogeneous nature of seeds and variability due to the extraction method, but almost in all cases, Δ9-THC concentrations were higher than the legal limit. These quantities of total Δ9-THC may reach as high as 3.8 mg per gram of hemp seeds, if one were consuming a 30-g daily recommended amount of hemp seeds, and is a cause for concern for potential toxicity. It is not clear if these high quantities of Δ9-THC are due to contamination of the seeds, or any other reason. Conclusion: Careful consideration of the extraction method is very important for the measurement of cannabinoids in hemp seeds.

Cannabinoids, Phenolics, Terpenes and Alkaloids of Cannabis / Mohamed M. Radwan, Suman Chandra, Shahbaz Gul, Mahmoud A. ElSohly

• Molecules 26 (2021) 9 (8 May), 2774, p. 1-29
• PMID: 34066753
• PMCID: PMC8125862
• DOI: 10.3390/molecules26092774

Abstract

Cannabis sativa is one of the oldest medicinal plants in the world. It was introduced into western medicine during the early 19th century. It contains a complex mixture of secondary metabolites, including cannabinoids and non-cannabinoid-type constituents. More than 500 compounds have been reported from C. sativa, of which 125 cannabinoids have been isolated and/or identified as cannabinoids. Cannabinoids are C21 terpeno-phenolic compounds specific to Cannabis. The non-cannabinoid constituents include: non-cannabinoid phenols, flavonoids, terpenes, alkaloids and others. This review discusses the chemistry of the cannabinoids and major non-cannabinoid constituents (terpenes, non-cannabinoid phenolics, and alkaloids) with special emphasis on their chemical structures, methods of isolation, and identification.